1932

Abstract

Mineralocorticoid receptor (MR) activation in the heart and vessels leads to pathological effects, such as excessive extracellular matrix accumulation, oxidative stress, and sustained inflammation. In these organs, the MR is expressed in cardiomyocytes, fibroblasts, endothelial cells, smooth muscle cells, and inflammatory cells. We review the accumulating experimental and clinical evidence that pharmacological MR antagonism has a positive impact on a battery of cardiac and vascular pathological states, including heart failure, myocardial infarction, arrhythmic diseases, atherosclerosis, vascular stiffness, and cardiac and vascular injury linked to metabolic comorbidities and chronic kidney disease. Moreover, we present perspectives on optimization of the use of MR antagonists in patients more likely to respond to such therapy and review the evidence suggesting that novel nonsteroidal MR antagonists offer an improved safety profile while retaining their cardiovascular protective effects. Finally, we highlight future therapeutic applications of MR antagonists in cardiovascular injury.

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2022-02-10
2024-03-28
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Literature Cited

  1. 1. 
    Jaisser F, Farman N. 2016. Emerging roles of the mineralocorticoid receptor in pathology: toward new paradigms in clinical pharmacology. Pharmacol. Rev. 68:49–75
    [Google Scholar]
  2. 2. 
    Barrera-Chimal J, Girerd S, Jaisser F. 2019. Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis. Kidney Int 96:302–19
    [Google Scholar]
  3. 3. 
    Buonafine M, Bonnard B, Jaisser F. 2018. Mineralocorticoid receptor and cardiovascular disease. Am. J. Hypertens. 31:1165–74
    [Google Scholar]
  4. 4. 
    Kolkhof P, Barfacker L. 2017. 30 years of the mineralocorticoid receptor. Mineralocorticoid receptor antagonists: 60 years of research and development. J. Endocrinol. 234:T125–40
    [Google Scholar]
  5. 5. 
    Agarwal R, Kolkhof P, Bakris G, Bauersachs J, Haller H et al. 2021. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur. Heart J. 42:152–61
    [Google Scholar]
  6. 6. 
    Brilla CG, Weber KT. 1992. Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. J. Lab. Clin. Med. 120:893–901
    [Google Scholar]
  7. 7. 
    Robert V, Van Thiem N, Cheav SL, Mouas C, Swynghedauw B, Delcayre C. 1994. Increased cardiac types I and III collagen mRNAs in aldosterone–salt hypertension. Hypertension 24:30–36
    [Google Scholar]
  8. 8. 
    Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A et al. 1999. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med. 341:709–17
    [Google Scholar]
  9. 9. 
    Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC et al. 2004. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N. Engl. J. Med. 351:543–51
    [Google Scholar]
  10. 10. 
    Pitt B, Remme W, Zannad F, Neaton J, Martinez F et al. 2003. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 348:1309–21
    [Google Scholar]
  11. 11. 
    Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K et al. 2011. Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 364:11–21
    [Google Scholar]
  12. 12. 
    Montalescot G, Pitt B, Lopez de Sa E, Hamm CW, Flather M et al. 2014. Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: the Randomized Double-Blind Reminder Study. Eur. Heart J. 35:2295–302
    [Google Scholar]
  13. 13. 
    Ferreira JP, Duarte K, Montalescot G, Pitt B, Lopez de Sa E et al. 2018. Effect of eplerenone on extracellular cardiac matrix biomarkers in patients with acute ST-elevation myocardial infarction without heart failure: insights from the randomized double-blind REMINDER study. Clin. Res. Cardiol. 107:49–59
    [Google Scholar]
  14. 14. 
    Ferreira JP, Duarte K, McMurray JJV, Pitt B, van Veldhuisen DJ et al. 2018. Data-driven approach to identify subgroups of heart failure with reduced ejection fraction patients with different prognoses and aldosterone antagonist response patterns. Circ. Heart Fail. 11:e004926
    [Google Scholar]
  15. 15. 
    Stienen S, Rossignol P, Barros A, Girerd N, Pitt B et al. 2020. Determinants of anti-fibrotic response to mineralocorticoid receptor antagonist therapy: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) and Early Eplerenone Treatment in Patients with Acute ST-elevation Myocardial Infarction without Heart Failure (REMINDER) trials. Clin. Res. Cardiol. 109:194–204
    [Google Scholar]
  16. 16. 
    Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS et al. 2014. Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 370:1383–92
    [Google Scholar]
  17. 17. 
    Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS et al. 2015. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Circulation 131:34–42
    [Google Scholar]
  18. 18. 
    Myhre PL, Vaduganathan M, O'Meara E, Claggett BL, de Denus S et al. 2020. Mechanistic effects of spironolactone on cardiovascular and renal biomarkers in heart failure with preserved ejection fraction: a TOPCAT biorepository study. Circ. Heart Fail. 13:e006638
    [Google Scholar]
  19. 19. 
    Cohen JB, Schrauben SJ, Zhao L, Basso MD, Cvijic ME et al. 2020. Clinical phenogroups in heart failure with preserved ejection fraction: detailed phenotypes, prognosis, and response to spironolactone. JACC Heart Fail 8:172–84
    [Google Scholar]
  20. 20. 
    Fukuta H, Goto T, Wakami K, Kamiya T, Ohte N 2019. Effects of mineralocorticoid receptor antagonists on left ventricular diastolic function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials. Heart Vessels 34:597–606
    [Google Scholar]
  21. 21. 
    Ravassa S, Trippel T, Bach D, Bachran D, Gonzalez A et al. 2018. Biomarker-based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: results from the Aldo-DHF trial. Eur. J. Heart Fail. 20:1290–99
    [Google Scholar]
  22. 22. 
    Beygui F, Cayla G, Roule V, Roubille F, Delarche N et al. 2016. Early aldosterone blockade in acute myocardial infarction: the ALBATROSS randomized clinical trial. J. Am. Coll. Cardiol. 67:1917–27
    [Google Scholar]
  23. 23. 
    Beygui F, Van Belle E, Ecollan P, Machecourt J, Hamm CW et al. 2018. Individual participant data analysis of two trials on aldosterone blockade in myocardial infarction. Heart 104:1843–49
    [Google Scholar]
  24. 24. 
    Secora AM, Shin JI, Qiao Y, Alexander GC, Chang AR et al. 2020. Hyperkalemia and acute kidney injury with spironolactone use among patients with heart failure. Mayo Clin. Proc. 95:2408–19
    [Google Scholar]
  25. 25. 
    Rossignol P, Dobre D, McMurray JJ, Swedberg K, Krum H et al. 2014. Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Circ. Heart Fail. 7:51–58
    [Google Scholar]
  26. 26. 
    Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G et al. 2013. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur. Heart J. 34:2453–63
    [Google Scholar]
  27. 27. 
    Wei J, Ni J, Huang D, Chen M, Yan S, Peng Y 2010. The effect of aldosterone antagonists for ventricular arrhythmia: a meta-analysis. Clin. Cardiol. 33:572–77
    [Google Scholar]
  28. 28. 
    Beygui F, Labbé JP, Cayla G, Ennezat PV, Motreff P et al. 2013. Early mineralocorticoid receptor blockade in primary percutaneous coronary intervention for ST-elevation myocardial infarction is associated with a reduction of life-threatening ventricular arrhythmia. Int. J. Cardiol. 167:73–79
    [Google Scholar]
  29. 29. 
    Rossello X, Ariti C, Pocock SJ, Ferreira JP, Girerd N et al. 2019. Impact of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with heart failure and left-ventricular systolic dysfunction: an individual patient-level meta-analysis of three randomized-controlled trials. Clin. Res. Cardiol. 108:477–86
    [Google Scholar]
  30. 30. 
    Neefs J, van den Berg NW, Limpens J, Berger WR, Boekholdt SM et al. 2017. Aldosterone pathway blockade to prevent atrial fibrillation: a systematic review and meta-analysis. Int. J. Cardiol. 231:155–61
    [Google Scholar]
  31. 31. 
    Swedberg K, Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ et al. 2012. Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. J. Am. Coll. Cardiol. 59:1598–603
    [Google Scholar]
  32. 32. 
    Neefs J, van den Berg NWE, Krul SPJ, Boekholdt SM, de Groot JR. 2020. Effect of spironolactone on atrial fibrillation in patients with heart failure with preserved ejection fraction: post-hoc analysis of the randomized, placebo-controlled TOPCAT trial. Am. J. Cardiovasc. Drugs 20:73–80
    [Google Scholar]
  33. 33. 
    Shantsila E, Shahid F, Sun Y, Deeks J, Calvert M et al. 2020. Spironolactone in atrial fibrillation with preserved cardiac fraction: the IMPRESS-AF trial. J. Am. Heart Assoc. 9:e016239
    [Google Scholar]
  34. 34. 
    Alexandre J, Ollitrault P, Fischer MO, Fellahi JL, Rozec B et al. 2019. Spironolactone and perioperative atrial fibrillation occurrence in cardiac surgery patients: rationale and design of the ALDOCURE trial. Am. Heart J. 214:88–96
    [Google Scholar]
  35. 35. 
    Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A et al. 2007. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 50:911–18
    [Google Scholar]
  36. 36. 
    Marzano L, Colussi G, Sechi LA, Catena C. 2015. Adrenalectomy is comparable with medical treatment for reduction of left ventricular mass in primary aldosteronism: meta-analysis of long-term studies. Am. J. Hypertens. 28:312–18
    [Google Scholar]
  37. 37. 
    Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A 2018. Incidence of atrial fibrillation and mineralocorticoid receptor activity in patients with medically and surgically treated primary aldosteronism. JAMA Cardiol 3:768–74
    [Google Scholar]
  38. 38. 
    Nagata K. 2008. Mineralocorticoid antagonism and cardiac hypertrophy. Curr. Hypertens. Rep. 10:216–21
    [Google Scholar]
  39. 39. 
    Sun Y, Zhang J, Lu L, Chen SS, Quinn MT, Weber KT 2002. Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am. J. Pathol. 161:1773–81
    [Google Scholar]
  40. 40. 
    Amador CA, Barrientos V, Pena J, Herrada AA, Gonzalez M et al. 2014. Spironolactone decreases DOCA-salt-induced organ damage by blocking the activation of T helper 17 and the downregulation of regulatory T lymphocytes. Hypertension 63:797–803
    [Google Scholar]
  41. 41. 
    Krebs CF, Lange S, Niemann G, Rosendahl A, Lehners A et al. 2014. Deficiency of the interleukin 17/23 axis accelerates renal injury in mice with deoxycorticosterone acetate+angiotensin II–induced hypertension. Hypertension 63:565–71
    [Google Scholar]
  42. 42. 
    Araos P, Prado C, Lozano M, Figueroa S, Espinoza A et al. 2019. Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase–associated lipocalin expression upon mineralocorticoid receptor activation. J. Hypertens. 37:1482–92
    [Google Scholar]
  43. 43. 
    Shao PP, Liu CJ, Xu Q, Zhang B, Li SH et al. 2018. Eplerenone reverses cardiac fibrosis via the suppression of Tregs by inhibition of Kv1.3 channel. Front. Physiol. 9:899
    [Google Scholar]
  44. 44. 
    Cai R, Hao Y, Liu YY, Huang L, Yao Y, Zhou MS. 2020. Tumor necrosis factor α deficiency improves endothelial function and cardiovascular injury in deoxycorticosterone acetate/salt-hypertensive mice. Biomed. Res. Int. 2020:3921074
    [Google Scholar]
  45. 45. 
    Di Zhang A, Cat AND, Soukaseum C, Escoubet B, Cherfa A et al. 2008. Cross-talk between mineralocorticoid and angiotensin II signaling for cardiac remodeling. Hypertension 52:1060–67
    [Google Scholar]
  46. 46. 
    Hu D, Dong R, Zhang Y, Yang Y, Chen Z et al. 2020. Age-related changes in mineralocorticoid receptors in rat hearts. Mol. Med. Rep. 22:1859–67
    [Google Scholar]
  47. 47. 
    Endemann DH, Touyz RM, Iglarz M, Savoia C, Schiffrin EL. 2004. Eplerenone prevents salt-induced vascular remodeling and cardiac fibrosis in stroke-prone spontaneously hypertensive rats. Hypertension 43:1252–57
    [Google Scholar]
  48. 48. 
    Oestreicher EM, Martinez-Vasquez D, Stone JR, Jonasson L, Roubsanthisuk W et al. 2003. Aldosterone and not plasminogen activator inhibitor 1 is a critical mediator of early angiotensin II/NG-nitro-l-arginine methyl ester-induced myocardial injury. Circulation 108:2517–23
    [Google Scholar]
  49. 49. 
    Kuster GM, Kotlyar E, Rude MK, Siwik DA, Liao R et al. 2005. Mineralocorticoid receptor inhibition ameliorates the transition to myocardial failure and decreases oxidative stress and inflammation in mice with chronic pressure overload. Circulation 111:420–27
    [Google Scholar]
  50. 50. 
    Ohtani T, Ohta M, Yamamoto K, Mano T, Sakata Y et al. 2007. Elevated cardiac tissue level of aldo-sterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292:R946–54
    [Google Scholar]
  51. 51. 
    Ibarrola J, Garaikoetxea M, Garcia-Peña A, Matilla L, Jover E et al. 2020. Beneficial effects of mineralocorticoid receptor antagonism on myocardial fibrosis in an experimental model of the myxomatous degeneration of the mitral valve. Int. J. Mol. Sci. 21:5372
    [Google Scholar]
  52. 52. 
    Tschope C, Van Linthout S, Jager S, Arndt R, Trippel T et al. 2020. Modulation of the acute defence reaction by eplerenone prevents cardiac disease progression in viral myocarditis. ESC Heart Fail 7:2838–52
    [Google Scholar]
  53. 53. 
    Yi Y, Du L, Qin M, Chen XQ, Sun XN et al. 2019. Regulation of atrial fibrosis by the bone. Hypertension 73:379–89
    [Google Scholar]
  54. 54. 
    Wang D, Liu YH, Yang XP, Rhaleb NE, Xu J et al. 2004. Role of a selective aldosterone blocker in mice with chronic heart failure. J. Card. Fail. 10:67–73
    [Google Scholar]
  55. 55. 
    Gueret A, Harouki N, Favre J, Galmiche G, Nicol L et al. 2016. Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction. Hypertension 67:717–23
    [Google Scholar]
  56. 56. 
    Kolkhof P, Delbeck M, Kretschmer A, Steinke W, Hartmann E et al. 2014. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J. Cardiovasc. Pharmacol. 64:69–78
    [Google Scholar]
  57. 57. 
    De Mello WC. 2006. Beneficial effect of eplerenone on cardiac remodelling and electrical properties of the failing heart. J. Renin-Angiotensin-Aldosterone Syst. 7:40–46
    [Google Scholar]
  58. 58. 
    Stein M, Boulaksil M, Jansen JA, Herold E, Noorman M et al. 2010. Reduction of fibrosis-related arrhythmias by chronic renin-angiotensin-aldosterone system inhibitors in an aged mouse model. Am. J. Physiol. Heart Circ. Physiol. 299:H310–21
    [Google Scholar]
  59. 59. 
    Deshmukh PA, Bellary SR, Schwender FT, Kamalov G, Magotra M et al. 2011. Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism. J. Cardiovasc. Pharmacol. 58:487–91
    [Google Scholar]
  60. 60. 
    Kimura S, Ito M, Tomita M, Hoyano M, Obata H et al. 2011. Role of mineralocorticoid receptor on atrial structural remodeling and inducibility of atrial fibrillation in hypertensive rats. Hypertens. Res. 34:584–91
    [Google Scholar]
  61. 61. 
    Zhao J, Li J, Li W, Li Y, Shan H et al. 2010. Effects of spironolactone on atrial structural remodelling in a canine model of atrial fibrillation produced by prolonged atrial pacing. Br. J. Pharmacol. 159:1584–94
    [Google Scholar]
  62. 62. 
    Youcef G, Olivier A, Nicot N, Muller A, Deng C et al. 2016. Preventive and chronic mineralocorticoid receptor antagonism is highly beneficial in obese SHHF rats. Br. J. Pharmacol. 173:1805–19
    [Google Scholar]
  63. 63. 
    Bender SB, DeMarco VG, Padilla J, Jenkins NT, Habibi J et al. 2015. Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction. Hypertension 65:1082–88
    [Google Scholar]
  64. 64. 
    Lachaux M, Barrera-Chimal J, Nicol L, Rémy-Jouet I, Renet S et al. 2018. Short- and long-term administration of the non-steroidal mineralocorticoid receptor antagonist finerenone opposes metabolic syndrome-related cardio-renal dysfunction. Diabetes Obes. Metab. 20:2399–407
    [Google Scholar]
  65. 65. 
    Guo C, Ricchiuti V, Lian BQ, Yao TM, Coutinho P et al. 2008. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor γ, and proinflammatory adipokines. Circulation 117:2253–61
    [Google Scholar]
  66. 66. 
    Bostick B, Habibi J, DeMarco VG, Jia G, Domeier TL et al. 2015. Mineralocorticoid receptor blockade prevents Western diet–induced diastolic dysfunction in female mice. Am. J. Physiol. Heart Circ. Physiol. 308:H1126–35
    [Google Scholar]
  67. 67. 
    Jia G, Habibi J, Aroor AR, Martinez-Lemus LA, DeMarco VG et al. 2016. Endothelial mineralocorticoid receptor mediates diet-induced aortic stiffness in females. Circ. Res. 118:935–43
    [Google Scholar]
  68. 68. 
    Liu W, Gong W, He M, Liu Y, Yang Y et al. 2018. Spironolactone protects against diabetic cardiomyopathy in streptozotocin-induced diabetic rats. J. Diabetes Res. 2018:9232065
    [Google Scholar]
  69. 69. 
    Mayyas F, Alzoubi KH, Bonyan R. 2017. The role of spironolactone on myocardial oxidative stress in rat model of streptozotocin-induced diabetes. Cardiovasc. Ther. 35:e12242
    [Google Scholar]
  70. 70. 
    Maron BA, Leopold JA. 2014. The role of the renin-angiotensin-aldosterone system in the pathobiology of pulmonary arterial hypertension (2013 Grover Conference series). Pulm. Circ. 4:200–10
    [Google Scholar]
  71. 71. 
    Omidkhoda N, Vakilian F, Mohammadpour AH, Sathyapalan T, Sahebkar A. 2020. Aldosterone and mineralocorticoid receptor antagonists on pulmonary hypertension and right ventricular failure: a review. Curr. Pharm. Des. 26:3862–70
    [Google Scholar]
  72. 72. 
    Preston IR, Sagliani KD, Warburton RR, Hill NS, Fanburg BL, Jaffe IZ. 2013. Mineralocorticoid receptor antagonism attenuates experimental pulmonary hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 304:L678–88
    [Google Scholar]
  73. 73. 
    Wang Y, Zhong B, Wu Q, Zhu T, Wang Y, Zhang M 2020. Aldosterone contributed to pulmonary arterial hypertension development via stimulating aquaporin expression and pulmonary arterial smooth muscle cells proliferation. Pharmacology 105:405–15
    [Google Scholar]
  74. 74. 
    Boehm M, Arnold N, Braithwaite A, Pickworth J, Lu C et al. 2018. Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension. BMC Pulm. Med. 18:41
    [Google Scholar]
  75. 75. 
    Wang Y, Zhong B, Wu Q, Tong J, Zhu T, Zhang M. 2020. Effect of aldosterone on senescence and proliferation inhibition of endothelial progenitor cells induced by sirtuin 1 (SIRT1) in pulmonary arterial hypertension. Med. Sci. Monit. 26:e920678
    [Google Scholar]
  76. 76. 
    Maron BA, Zhang YY, White K, Chan SY, Handy DE et al. 2012. Aldosterone inactivates the endothelin-B receptor via a cysteinyl thiol redox switch to decrease pulmonary endothelial nitric oxide levels and modulate pulmonary arterial hypertension. Circulation 126:963–74
    [Google Scholar]
  77. 77. 
    Kowalski J, Deng L, Suennen C, Koca D, Meral D et al. 2021. Eplerenone improves pulmonary vascular remodeling and hypertension by inhibition of the mineralocorticoid receptor in endothelial cells. Hypertension 78:456–65
    [Google Scholar]
  78. 78. 
    Barrera-Chimal J, Jaisser F. 2021. Mineralocorticoid receptor in endothelial cells, a major contributor in pulmonary arterial hypertension remodeling. Hypertension 78:466–68
    [Google Scholar]
  79. 79. 
    Ouvrard-Pascaud A, Sainte-Marie Y, Benitah JP, Perrier R, Soukaseum C et al. 2005. Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Circulation 111:3025–33
    [Google Scholar]
  80. 80. 
    Mesquita TR, Auguste G, Falcón D, Ruiz-Hurtado G, Salazar-Enciso R et al. 2018. Specific activation of the alternative cardiac promoter of Cacna1c by the mineralocorticoid receptor. Circ. Res. 122:e49–61
    [Google Scholar]
  81. 81. 
    Koyama R, Mannic T, Ito J, Amar L, Zennaro MC et al. 2018. MicroRNA-204 is necessary for aldosterone-stimulated T-type calcium channel expression in cardiomyocytes. Int. J. Mol. Sci. 19:2941
    [Google Scholar]
  82. 82. 
    Favre J, Gao J, Zhang AD, Rémy-Jouet I, Ouvrard-Pascaud A et al. 2011. Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression. Am. J. Physiol. Heart Circ. Physiol. 300:H2035–43
    [Google Scholar]
  83. 83. 
    Ennis IL, Pérez NG. 2020. Cardiac mineralocorticoid receptor and the Na+/H+ exchanger: spilling the beans. Front. Cardiovasc. Med. 7:614279
    [Google Scholar]
  84. 84. 
    Messaoudi S, Gravez B, Tarjus A, Pelloux V, Ouvrard-Pascaud A et al. 2013. Aldosterone-specific activation of cardiomyocyte mineralocorticoid receptor in vivo. Hypertension 61:361–67
    [Google Scholar]
  85. 85. 
    Latouche C, El Moghrabi S, Messaoudi S, Cat AND, Hernandez-Diaz I et al. 2012. Neutrophil gelatinase–associated lipocalin is a novel mineralocorticoid target in the cardiovascular system. Hypertension 59:966–72
    [Google Scholar]
  86. 86. 
    Tarjus A, Martínez-Martínez E, Amador C, Latouche C, El Moghrabi S et al. 2015. Neutrophil gelatinase–associated lipocalin, a novel mineralocorticoid biotarget, mediates vascular profibrotic effects of mineralocorticoids. Hypertension 66:158–66
    [Google Scholar]
  87. 87. 
    López-Andrés N, Martin-Fernandez B, Rossignol P, Zannad F, Lahera V et al. 2011. A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone. Am. J. Physiol. Heart Circ. Physiol. 301:H2372–82
    [Google Scholar]
  88. 88. 
    Rickard AJ, Morgan J, Bienvenu LA, Fletcher EK, Cranston GA et al. 2012. Cardiomyocyte mineralocorticoid receptors are essential for deoxycorticosterone/salt-mediated inflammation and cardiac fibrosis. Hypertension 60:1443–50
    [Google Scholar]
  89. 89. 
    Fletcher EK, Kanki M, Morgan J, Ray DW, Delbridge L et al. 2019. Cardiomyocyte transcription is controlled by combined MR and circadian clock signalling. J. Endocrinol. 241:17–29
    [Google Scholar]
  90. 90. 
    Fletcher EK, Morgan J, Kennaway DR, Bienvenu LA, Rickard AJ et al. 2017. Deoxycorticosterone/salt-mediated cardiac inflammation and fibrosis are dependent on functional CLOCK signaling in male mice. Endocrinology 158:2906–17
    [Google Scholar]
  91. 91. 
    Kim SK, Biwer LA, Moss ME, Man JJ, Aronovitz MJ et al. 2021. Mineralocorticoid receptor in smooth muscle contributes to pressure overload–induced heart failure. Circ. Heart Fail. 14:e007279
    [Google Scholar]
  92. 92. 
    DuPont JJ, Kim SK, Kenney RM, Jaffe IZ. 2021. Sex differences in the time course and mechanisms of vascular and cardiac aging in mice: role of the smooth muscle cell mineralocorticoid receptor. Am. J. Physiol. Heart Circ. Physiol. 320:H169–80
    [Google Scholar]
  93. 93. 
    Lother A, Furst D, Bergemann S, Gilsbach R, Grahammer F et al. 2016. Deoxycorticosterone acetate/salt-induced cardiac but not renal injury is mediated by endothelial mineralocorticoid receptors independently from blood pressure. Hypertension 67:130–38
    [Google Scholar]
  94. 94. 
    Lother A, Deng L, Huck M, Furst D, Kowalski J et al. 2019. Endothelial cell mineralocorticoid receptors oppose VEGF-induced gene expression and angiogenesis. J. Endocrinol. 240:15–26
    [Google Scholar]
  95. 95. 
    Salvador AM, Moss ME, Aronovitz M, Mueller KB, Blanton RM et al. 2017. Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation. Physiol. Rep. 5:e13313
    [Google Scholar]
  96. 96. 
    Ibarrola J, Garcia-Peña A, Matilla L, Bonnard B, Sadaba R et al. 2020. A new role for the aldosterone/mineralocorticoid receptor pathway in the development of mitral valve prolapse. Circ. Res. 127:e80–93
    [Google Scholar]
  97. 97. 
    Usher MG, Duan SZ, Ivaschenko CY, Frieler RA, Berger S et al. 2010. Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J. Clin. Investig. 120:3350–64
    [Google Scholar]
  98. 98. 
    Li C, Zhang YY, Frieler RA, Zheng XJ, Zhang WC et al. 2014. Myeloid mineralocorticoid receptor deficiency inhibits aortic constriction–induced cardiac hypertrophy in mice. PLOS ONE 9:e110950
    [Google Scholar]
  99. 99. 
    Fraccarollo D, Thomas S, Scholz CJ, Hilfiker-Kleiner D, Galuppo P, Bauersachs J 2019. Macrophage mineralocorticoid receptor is a pleiotropic modulator of myocardial infarct healing. Hypertension 73:102–11
    [Google Scholar]
  100. 100. 
    Li C, Sun XN, Zeng MR, Zheng XJ, Zhang YY et al. 2017. Mineralocorticoid receptor deficiency in T cells attenuates pressure overload–induced cardiac hypertrophy and dysfunction through modulating T cell activation. Hypertension 70:137–47
    [Google Scholar]
  101. 101. 
    Sun XN, Li C, Liu Y, Du LJ, Zeng MR et al. 2017. T-cell mineralocorticoid receptor controls blood pressure by regulating interferon-γ. Circ. Res. 120:1584–97
    [Google Scholar]
  102. 102. 
    Stockand JD, Meszaros JG. 2003. Aldosterone stimulates proliferation of cardiac fibroblasts by activating Ki-RasA and MAPK1/2 signaling. Am. J. Physiol. Heart Circ. Physiol. 284:H176–84
    [Google Scholar]
  103. 103. 
    Wang Q, Cui W, Zhang HL, Hu HJ, Zhang YN et al. 2013. Atorvastatin suppresses aldosterone-induced neonatal rat cardiac fibroblast proliferation by inhibiting ERK1/2 in the genomic pathway. J. Cardiovasc. Pharmacol. 61:520–27
    [Google Scholar]
  104. 104. 
    Martínez-Martínez E, Calvier L, Fernández-Celis A, Rousseau E, Jurado-López R et al. 2015. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension. Hypertension 66:767–75
    [Google Scholar]
  105. 105. 
    Martinez-Martinez E, Buonafine M, Boukhalfa I, Ibarrola J, Fernández-Celis A et al. 2017. Aldosterone target NGAL (neutrophil gelatinase–associated lipocalin) is involved in cardiac remodeling after myocardial infarction through NFκB pathway. Hypertension 70:1148–56
    [Google Scholar]
  106. 106. 
    Lavall D, Selzer C, Schuster P, Lenski M, Adam O et al. 2014. The mineralocorticoid receptor promotes fibrotic remodeling in atrial fibrillation. J. Biol. Chem. 289:6656–68
    [Google Scholar]
  107. 107. 
    Lother A, Berger S, Gilsbach R, Rösner S, Ecke A et al. 2011. Ablation of mineralocorticoid receptors in myocytes but not in fibroblasts preserves cardiac function. Hypertension 57:746–54
    [Google Scholar]
  108. 108. 
    Li W, Chen X, Riley AM, Hiett SC, Temm CJ et al. 2017. Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs. Basic Res. Cardiol. 112:54
    [Google Scholar]
  109. 109. 
    Kratz MT, Schirmer SH, Baumhakel M, Bohm M. 2016. Improvement of endothelial function in a murine model of mild cholesterol-induced atherosclerosis by mineralocorticoid antagonism. Atherosclerosis 251:291–98
    [Google Scholar]
  110. 110. 
    Marzolla V, Armani A, Mammi C, Moss ME, Pagliarini V et al. 2017. Essential role of ICAM-1 in aldosterone-induced atherosclerosis. Int. J. Cardiol. 232:233–42
    [Google Scholar]
  111. 111. 
    Marzolla V, Armani A, Mammi C, Feraco A, Caprio M 2018. Induction of atherosclerotic plaques through activation of mineralocorticoid receptors in apolipoprotein E–deficient mice. J. Vis. Exp. 139:58303
    [Google Scholar]
  112. 112. 
    Caprio M, Newfell BG, La Sala A, Baur W, Fabbri A et al. 2008. Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule 1 expression and promote leukocyte adhesion. Circ. Res. 102:1359–67
    [Google Scholar]
  113. 113. 
    Moss ME, Lu Q, Iyer SL, Engelbertsen D, Marzolla V et al. 2019. Endothelial mineralocorticoid receptors contribute to vascular inflammation in atherosclerosis in a sex-specific manner. Arterioscler. Thromb. Vasc. Biol. 39:1588–601
    [Google Scholar]
  114. 114. 
    Moss ME, DuPont JJ, Iyer SL, McGraw AP, Jaffe IZ. 2018. No significant role for smooth muscle cell mineralocorticoid receptors in atherosclerosis in the apolipoprotein-E knockout mouse model. Front. Cardiovasc. Med. 5:81
    [Google Scholar]
  115. 115. 
    Shen ZX, Chen XQ, Sun XN, Sun JY, Zhang WC et al. 2017. Mineralocorticoid receptor deficiency in macrophages inhibits atherosclerosis by affecting foam cell formation and efferocytosis. J. Biol. Chem. 292:925–35
    [Google Scholar]
  116. 116. 
    Sun JY, Li C, Shen ZX, Zhang WC, Ai TJ et al. 2016. Mineralocorticoid receptor deficiency in macrophages inhibits neointimal hyperplasia and suppresses macrophage inflammation through SGK1-AP1/NF-κB pathways. Arterioscler. Thromb. Vasc. Biol. 36:874–85
    [Google Scholar]
  117. 117. 
    Zhao M, Mantel I, Gelize E, Li X, Xie X et al. 2019. Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration. Nat. Commun. 10:369
    [Google Scholar]
  118. 118. 
    Kim SK, McCurley AT, DuPont JJ, Aronovitz M, Moss ME et al. 2018. Smooth muscle cell–mineralocorticoid receptor as a mediator of cardiovascular stiffness with aging. Hypertension 71:609–21
    [Google Scholar]
  119. 119. 
    Lu Q, Davel AP, McGraw AP, Rao SP, Newfell BG, Jaffe IZ. 2019. PKCδ mediates mineralocorticoid receptor activation by angiotensin II to modulate smooth muscle cell function. Endocrinology 160:2101–14
    [Google Scholar]
  120. 120. 
    DuPont JJ, McCurley A, Davel AP, McCarthy J, Bender SB et al. 2016. Vascular mineralocorticoid receptor regulates microRNA-155 to promote vasoconstriction and rising blood pressure with aging. JCI Insight 1:e88942
    [Google Scholar]
  121. 121. 
    Sakima A, Arima H, Matayoshi T, Ishida A, Ohya Y. 2021. Effect of mineralocorticoid receptor blockade on arterial stiffness and endothelial function: a meta-analysis of randomized trials. Hypertension 77:929–37
    [Google Scholar]
  122. 122. 
    Galmiche G, Pizard A, Gueret A, El Moghrabi S, Ouvrard-Pascaud A et al. 2014. Smooth muscle cell mineralocorticoid receptors are mandatory for aldosterone-salt to induce vascular stiffness. Hypertension 63:520–26
    [Google Scholar]
  123. 123. 
    Liu S, Xie Z, Daugherty A, Cassis LA, Pearson KJ et al. 2013. Mineralocorticoid receptor agonists induce mouse aortic aneurysm formation and rupture in the presence of high salt. Arterioscler. Thromb. Vasc. Biol. 33:1568–79
    [Google Scholar]
  124. 124. 
    Yan Y, Wang C, Lu Y, Gong H, Wu Z et al. 2018. Mineralocorticoid receptor antagonism protects the aorta from vascular smooth muscle cell proliferation and collagen deposition in a rat model of adrenal aldosterone-producing adenoma. J. Physiol. Biochem. 74:17–24
    [Google Scholar]
  125. 125. 
    Jaffe IZ, Tintut Y, Newfell BG, Demer LL, Mendelsohn ME. 2007. Mineralocorticoid receptor activation promotes vascular cell calcification. Arterioscler. Thromb. Vasc. Biol. 27:799–805
    [Google Scholar]
  126. 126. 
    Lang F, Ritz E, Alesutan I, Voelkl J 2014. Impact of aldosterone on osteoinductive signaling and vascular calcification. Nephron Physiol 128:40–45
    [Google Scholar]
  127. 127. 
    Alesutan I, Voelkl J, Feger M, Kratschmar DV, Castor T et al. 2017. Involvement of vascular aldo-sterone synthase in phosphate-induced osteogenic transformation of vascular smooth muscle cells. Sci. Rep. 7:2059
    [Google Scholar]
  128. 128. 
    Hao J, Tang J, Zhang L, Li X, Hao L 2020. The crosstalk between calcium ions and aldosterone contributes to inflammation, apoptosis, and calcification of VSMC via the AIF-1/NF-κB pathway in uremia. Oxid. Med. Cell. Longev. 2020:3431597
    [Google Scholar]
  129. 129. 
    Tatsumoto N, Yamada S, Tokumoto M, Eriguchi M, Noguchi H et al. 2015. Spironolactone ameliorates arterial medial calcification in uremic rats: the role of mineralocorticoid receptor signaling in vascular calcification. Am. J. Physiol. Ren. Physiol. 309:F967–79
    [Google Scholar]
  130. 130. 
    Voelkl J, Alesutan I, Leibrock CB, Quintanilla-Martinez L, Kuhn V et al. 2013. Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice. J. Clin. Investig. 123:812–22
    [Google Scholar]
  131. 131. 
    Zhu D, Rashdan NA, Chapman KE, Hadoke PW, MacRae VE. 2016. A novel role for the mineralocorticoid receptor in glucocorticoid driven vascular calcification. Vascul. Pharmacol. 86:87–93
    [Google Scholar]
  132. 132. 
    DeMarco VG, Habibi J, Jia G, Aroor AR, Ramirez-Perez FI et al. 2015. Low-dose mineralocorticoid receptor blockade prevents Western diet–induced arterial stiffening in female mice. Hypertension 66:99–107
    [Google Scholar]
  133. 133. 
    Aroor AR, Habibi J, Nistala R, Ramirez-Perez FI, Martinez-Lemus LA et al. 2019. Diet-induced obesity promotes kidney endothelial stiffening and fibrosis dependent on the endothelial mineralocorticoid receptor. Hypertension 73:849–58
    [Google Scholar]
  134. 134. 
    Davel AP, Lu Q, Moss ME, Rao S, Anwar IJ et al. 2018. Sex-specific mechanisms of resistance vessel endothelial dysfunction induced by cardiometabolic risk factors. J. Am. Heart Assoc. 7:e007675
    [Google Scholar]
  135. 135. 
    Huby AC, Otvos L Jr., Belin de Chantemele EJ. 2016. Leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in obese female mice. Hypertension 67:1020–28
    [Google Scholar]
  136. 136. 
    Silva MAB, Bruder-Nascimento T, Cau SBA, Lopes RAM, Mestriner FLAC et al. 2015. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling. Front. Physiol. 6:269
    [Google Scholar]
  137. 137. 
    Cat AND, Callera GE, Friederich-Persson M, Sanchez A, Dulak-Lis MG et al. 2018. Vascular dysfunction in obese diabetic db/db mice involves the interplay between aldosterone/mineralocorticoid receptor and Rho kinase signaling. Sci. Rep. 8:2952
    [Google Scholar]
  138. 138. 
    Lefranc C, Friederich-Persson M, Braud L, Palacios-Ramirez R, Karlsson S et al. 2019. MR (mineralocorticoid receptor) induces adipose tissue senescence and mitochondrial dysfunction leading to vascular dysfunction in obesity. Hypertension 73:458–68
    [Google Scholar]
  139. 139. 
    Briet M, Schiffrin EL. 2011. The role of aldosterone in the metabolic syndrome. Curr. Hypertens. Rep. 13:163–72
    [Google Scholar]
  140. 140. 
    Bruder-Nascimento T, da Silva MA, Tostes RC. 2014. The involvement of aldosterone on vascular insulin resistance: implications in obesity and type 2 diabetes. Diabetol. Metab. Syndr. 6:90
    [Google Scholar]
  141. 141. 
    Wang J, Hu H, Song J, Yan F, Qin J et al. 2019. Aldosterone induced up-expression of ICAM-1 and ET-1 in pancreatic islet endothelium may associate with progression of T2D. Biochem. Biophys. Res. Commun. 512:750–57
    [Google Scholar]
  142. 142. 
    Brown SM, Meuth AI, Davis JW, Rector RS, Bender SB. 2018. Mineralocorticoid receptor antagonism reverses diabetes-related coronary vasodilator dysfunction: a unique vascular transcriptomic signature. Pharmacol. Res. 134:100–08
    [Google Scholar]
  143. 143. 
    Schäfer N, Lohmann C, Winnik S, van Tits LJ, Miranda MX et al. 2013. Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity. Eur. Heart J. 34:3515–24
    [Google Scholar]
  144. 144. 
    Pires PW, McClain JL, Hayoz SF, Dorrance AM. 2018. Mineralocorticoid receptor antagonism prevents obesity-induced cerebral artery remodeling and reduces white matter injury in rats. Microcirculation 25:e12460
    [Google Scholar]
  145. 145. 
    Diaz-Otero JM, Yen TC, Fisher C, Bota D, Jackson WF, Dorrance AM 2018. Mineralocorticoid receptor antagonism improves parenchymal arteriole dilation via a TRPV4-dependent mechanism and prevents cognitive dysfunction in hypertension. Am. J. Physiol. Heart Circ. Physiol. 315:H1304–15
    [Google Scholar]
  146. 146. 
    Michea L, Villagran A, Urzua A, Kuntsmann S, Venegas P et al. 2008. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and prevents oxidative stress in uremic rats. Hypertension 52:295–300
    [Google Scholar]
  147. 147. 
    Bonnard B, Pieronne-Deperrois M, Djerada Z, Elmoghrabi S, Kolkhof P et al. 2018. Mineralocorticoid receptor antagonism improves diastolic dysfunction in chronic kidney disease in mice. J. Mol. Cell Cardiol. 121:124–33
    [Google Scholar]
  148. 148. 
    Gil-Ortega M, Vega-Martín E, Martín-Ramos M, González-Blázquez R, Pulido-Olmo H et al. 2020. Finerenone reduces intrinsic arterial stiffness in Munich Wistar Frömter rats, a genetic model of chronic kidney disease. Am. J. Nephrol. 51:294–303
    [Google Scholar]
  149. 149. 
    Wang CC, Lee AS, Liu SH, Chang KC, Shen MY, Chang CT. 2019. Spironolactone ameliorates endothelial dysfunction through inhibition of the AGE/RAGE axis in a chronic renal failure rat model. BMC Nephrol 20:351
    [Google Scholar]
  150. 150. 
    Edwards NC, Steeds RP, Stewart PM, Ferro CJ, Townend JN. 2009. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J. Am. Coll. Cardiol. 54:505–12
    [Google Scholar]
  151. 151. 
    Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD et al. 2020. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst. Rev. 10:CD007004
    [Google Scholar]
  152. 152. 
    Quach K, Lvtvyn L, Baigent C, Bueti J, Garg AX et al. 2016. The safety and efficacy of mineralocorticoid receptor antagonists in patients who require dialysis: a systematic review and meta-analysis. Am. J. Kidney Dis. 68:591–98
    [Google Scholar]
  153. 153. 
    Charytan DM, Himmelfarb J, Ikizler TA, Raj DS, Hsu JY et al. 2019. Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. Kidney Int 95:973–82
    [Google Scholar]
  154. 154. 
    Rossignol P, Frimat L, Zannad F. 2019. The safety of mineralocorticoid antagonists in maintenance hemodialysis patients: two steps forward. Kidney Int 95:747–49
    [Google Scholar]
  155. 155. 
    Hill NR, Lasserson D, Thompson B, Perera-Salazar R, Wolstenholme J et al. 2014. Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D) trial—a multi-centre, prospective, randomised, open, blinded end-point, 36-month study of 2,616 patients within primary care with stage 3b chronic kidney disease to compare the efficacy of spironolactone 25 mg once daily in addition to routine care on mortality and cardiovascular outcomes versus routine care alone: study protocol for a randomized controlled trial. Trials 15:160
    [Google Scholar]
  156. 156. 
    Beldhuis IE, Myhre PL, Claggett B, Damman K, Fang JC et al. 2019. Efficacy and safety of spironolactone in patients with HFpEF and chronic kidney disease. JACC Heart Fail 7:25–32
    [Google Scholar]
  157. 157. 
    Rossignol P, Cleland JG, Bhandari S, Tala S, Gustafsson F et al. 2012. Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. Circulation 125:271–79
    [Google Scholar]
  158. 158. 
    Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM et al. 2020. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N. Engl. J. Med. 383:2219–29
    [Google Scholar]
  159. 159. 
    Filippatos G, Anker SD, Agarwal R, Pitt B, Ruilope LM et al. 2021. Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. Circulation 143:540–52
    [Google Scholar]
  160. 160. 
    Ruilope LM, Agarwal R, Anker SD, Bakris GL, Filippatos G et al. 2019. Design and baseline characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial. Am. J. Nephrol. 50:345–56
    [Google Scholar]
  161. 161. 
    Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL et al. 2021. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N. Engl. J. Med. 385:2252–63
    [Google Scholar]
  162. 162. 
    Kolkhof P, Borden SA. 2012. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. Mol. Cell Endocrinol. 350:310–17
    [Google Scholar]
  163. 163. 
    Amazit L, Le Billan F, Kolkhof P, Lamribet K, Viengchareun S et al. 2015. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator 1. J. Biol. Chem. 290:21876–89
    [Google Scholar]
  164. 164. 
    Bamberg K, Johansson U, Edman K, William-Olsson L, Myhre S et al. 2018. Preclinical pharmacology of AZD9977: a novel mineralocorticoid receptor modulator separating organ protection from effects on electrolyte excretion. PLOS ONE 13:e0193380
    [Google Scholar]
  165. 165. 
    Grune J, Benz V, Brix S, Salatzki J, Blumrich A et al. 2016. Steroidal and nonsteroidal mineralocorticoid receptor antagonists cause differential cardiac gene expression in pressure overload-induced cardiac hypertrophy. J. Cardiovasc. Pharmacol. 67:402–11
    [Google Scholar]
  166. 166. 
    Grune J, Beyhoff N, Smeir E, Chudek R, Blumrich A et al. 2018. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone's antifibrotic activity. Hypertension 71:599–608
    [Google Scholar]
  167. 167. 
    Mihailidou AS, Tzakos AG, Ashton AW. 2019. Non-genomic effects of aldosterone. Vitam. Horm. 109:133–49
    [Google Scholar]
  168. 168. 
    Harvey BJ, Thomas W. 2018. Aldosterone-induced protein kinase signalling and the control of electrolyte balance. Steroids 133:67–74
    [Google Scholar]
  169. 169. 
    Faresse N. 2014. Post-translational modifications of the mineralocorticoid receptor: how to dress the receptor according to the circumstances?. J. Steroid Biochem. Mol. Biol. 143:334–42
    [Google Scholar]
  170. 170. 
    Maggioni AP, Anker SD, Dahlström U, Filippatos G, Ponikowski P et al. 2013. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur. J. Heart Fail. 15:1173–84
    [Google Scholar]
  171. 171. 
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF et al. 2016. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 37:2129–200
    [Google Scholar]
  172. 172. 
    Williams B, Mancia G, Spiering W, Rosei EA, Azizi M et al. 2018. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur. Heart J. 39:3021–104
    [Google Scholar]
  173. 173. 
    Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP et al. 2018. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF Registry. J. Am. Coll. Cardiol. 72:351–66
    [Google Scholar]
  174. 174. 
    Weir MR, Bushinsky DA, Benton WW, Woods SD, Mayo MR et al. 2018. Effect of patiromer on hyperkalemia recurrence in older chronic kidney disease patients taking RAAS inhibitors. Am. J. Med. 131:555–64.e3
    [Google Scholar]
  175. 175. 
    Rakugi H, Ito S, Itoh H, Okuda Y, Yamakawa S. 2019. Long-term phase 3 study of esaxerenone as mono or combination therapy with other antihypertensive drugs in patients with essential hypertension. Hypertens. Res. 42:1932–41
    [Google Scholar]
  176. 176. 
    Rossing P, Persson F, Frimodt-Møller M, Hansen TW. 2021. Linking kidney and cardiovascular complications in diabetes-impact on prognostication and treatment: the 2019 Edwin Bierman Award lecture. Diabetes 70:39–50
    [Google Scholar]
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