1932

Abstract

Cells of the vascular wall are exquisitely sensitive to changes in their mechanical environment. In healthy vessels, mechanical forces regulate signaling and gene expression to direct the remodeling needed for the vessel wall to maintain optimal function. Major diseases of arteries involve maladaptive remodeling with compromised or lost homeostatic mechanisms. Whereas homeostasis invokes negative feedback loops at multiple scales to mediate mechanobiological stability, disease progression often occurs via positive feedback that generates mechanobiological instabilities. In this review, we focus on the cell biology, wall mechanics, and regulatory pathways associated with arterial health and how changes in these processes lead to disease. We discuss how positive feedback loops arise via biomechanical and biochemical means. We conclude that inflammation plays a central role in overriding homeostatic pathways and suggest future directions for addressing therapeutic needs.

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2021-07-13
2024-05-12
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Literature Cited

  1. 1. 
    Dajnowiec D, Langille BL. 2007. Arterial adaptations to chronic changes in haemodynamic function: coupling vasomotor tone to structural remodelling. Clin. Sci. 113:15–23
    [Google Scholar]
  2. 2. 
    Bikfalvi A. 2006. Angiogenesis: health and disease. Ann. Oncol. 17:Suppl. 10x65–70
    [Google Scholar]
  3. 3. 
    Humphrey JD, Dufresne ER, Schwartz MA. 2014. Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol. 15:802–12
    [Google Scholar]
  4. 4. 
    Safar ME. 2010. Arterial aging—hemodynamic changes and therapeutic options. Nat. Rev. Cardiol. 7:442–49
    [Google Scholar]
  5. 5. 
    Humphrey JD. 2002. Cardiovascular Solid Mechanics: Cells, Tissues, and Organs New York: Springer758 pp.
  6. 6. 
    Davies PF. 2009. Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat. Clin. Pract. Cardiovasc. Med. 6:16–26
    [Google Scholar]
  7. 7. 
    Humphrey JD. 2008. Mechanisms of arterial remodeling in hypertension: coupled roles of wall shear and intramural stress. Hypertension 52:195–200
    [Google Scholar]
  8. 8. 
    Humphrey JD, Eberth JF, Dye WW, Gleason RL. 2009. Fundamental role of axial stress in compensatory adaptations by arteries. J. Biomech. 42:1–8
    [Google Scholar]
  9. 9. 
    Holzapfel GA, Ogden RW. 2010. Modelling the layer-specific three-dimensional residual stresses in arteries, with an application to the human aorta. J. R. Soc. Interface 7:787–99
    [Google Scholar]
  10. 10. 
    Claesson-Welsh L. 2015. Vascular permeability—the essentials. Upsala J. Med. Sci. 120:135–43
    [Google Scholar]
  11. 11. 
    Wettschureck N, Strilic B, Offermanns S. 2019. Passing the vascular barrier: endothelial signaling processes controlling extravasation. Physiol. Rev. 99:1467–525
    [Google Scholar]
  12. 12. 
    Zhou J, Li YS, Chien S. 2014. Shear stress–initiated signaling and its regulation of endothelial function. Arterioscler. Thromb. Vasc. Biol. 34:2191–98
    [Google Scholar]
  13. 13. 
    Baratchi S, Khoshmanesh K, Woodman OL, Potocnik S, Peter K, McIntyre P. 2017. Molecular sensors of blood flow in endothelial cells. Trends Mol. Med. 23:850–68
    [Google Scholar]
  14. 14. 
    Tsao PS, Buitrago R, Chan JR, Cooke JP. 1996. Fluid flow inhibits endothelial adhesiveness: nitric oxide and transcriptional regulation of VCAM-1. Circulation 94:1682–89
    [Google Scholar]
  15. 15. 
    Baeyens N, Nicoli S, Coon BG, Ross TD, Van den Dries K et al. 2015. Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. eLife 4:e04645
    [Google Scholar]
  16. 16. 
    Fang JS, Coon BG, Gillis N, Chen Z, Qiu J et al. 2017. Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification. Nat. Commun. 8:2149
    [Google Scholar]
  17. 17. 
    Mohan S, Mohan N, Sprague EA. 1997. Differential activation of NF-κB in human aortic endothelial cells conditioned to specific flow environments. Am. J. Physiol. Cell Physiology 273:C572–78
    [Google Scholar]
  18. 18. 
    Mohan S, Mohan N, Valente AJ, Sprague EA. 1999. Regulation of low shear flow–induced HAEC VCAM-1 expression and monocyte adhesion. Am. J. Physiol. Cell Physiology 276:C1100–7
    [Google Scholar]
  19. 19. 
    Scholz D, Ito W, Fleming I, Deindl E, Sauer A et al. 2000. Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis). Virch. Arch. 436:257–70
    [Google Scholar]
  20. 20. 
    Yuan S, Yurdagul A Jr., Peretik JM, Alfaidi M, Al Yafeai Z et al. 2018. Cystathionine γ-lyase modulates flow-dependent vascular remodeling. Arterioscler. Thromb. Vasc. Biol. 38:2126–36
    [Google Scholar]
  21. 21. 
    Schaper W. 2009. Collateral circulation: past and present. Basic Res. Cardiol. 104:5–21
    [Google Scholar]
  22. 22. 
    Malek A, Izumo S. 1992. Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium. Am. J. Physiol. Cell Physiology 263:C389–96
    [Google Scholar]
  23. 23. 
    Uematsu M, Ohara Y, Navas JP, Nishida K, Murphy TJ et al. 1995. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am. J. Physiol. Cell Physiology 269:C1371–78
    [Google Scholar]
  24. 24. 
    Chiu JJ, Wang DL, Chien S, Skalak R, Usami S. 1998. Effects of disturbed flow on endothelial cells. J. Biomech. Eng. 120:2–8
    [Google Scholar]
  25. 25. 
    Baeyens N, Bandyopadhyay C, Coon BG, Yun S, Schwartz MA 2016. Endothelial fluid shear stress sensing in vascular health and disease. J. Clin. Investig. 126:821–28
    [Google Scholar]
  26. 26. 
    Owens GK, Kumar MS, Wamhoff BR. 2004. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol. Rev. 84:767–801
    [Google Scholar]
  27. 27. 
    Haga JH, Li YS, Chien S. 2007. Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells. J. Biomech. 40:947–60
    [Google Scholar]
  28. 28. 
    Lacolley P, Regnault V, Segers P, Laurent S. 2017. Vascular smooth muscle cells and arterial stiffening: relevance in development, aging, and disease. Physiol. Rev. 97:1555–617
    [Google Scholar]
  29. 29. 
    Leung DY, Glagov S, Mathews MB. 1976. Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. Science 191:475–77
    [Google Scholar]
  30. 30. 
    Wilson E, Sudhir K, Ives HE. 1995. Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. J. Clin. Investig. 96:2364–72
    [Google Scholar]
  31. 31. 
    Goldschmidt ME, McLeod KJ, Taylor WR. 2001. Integrin-mediated mechanotransduction in vascular smooth muscle cells: frequency and force response characteristics. Circ. Res. 88:674–80
    [Google Scholar]
  32. 32. 
    Leckband DE, de Rooij J. 2014. Cadherin adhesion and mechanotransduction. Annu. Rev. Cell Dev. Biol. 30:291–315
    [Google Scholar]
  33. 33. 
    Cao W, Zhang D, Li Q, Liu Y, Jing S et al. 2017. Biomechanical stretch induces inflammation, proliferation, and migration by activating NFAT5 in arterial smooth muscle cells. Inflammation 40:2129–36
    [Google Scholar]
  34. 34. 
    Wang Y, Cao W, Cui J, Yu Y, Zhao Y et al. 2018. Arterial wall stress induces phenotypic switching of arterial smooth muscle cells in vascular remodeling by activating the YAP/TAZ signaling pathway. Cell. Physiol. Biochem. 51:842–53
    [Google Scholar]
  35. 35. 
    Strauss BH, Rabinovitch M. 2000. Adventitial fibroblasts: defining a role in vessel wall remodeling. Am. J. Respir. Cell Mol. Biol. 22:1–3
    [Google Scholar]
  36. 36. 
    Sartore S, Chiavegato A, Faggin E, Franch R, Puato M et al. 2001. Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: from innocent bystander to active participant. Circ. Res. 89:1111–21
    [Google Scholar]
  37. 37. 
    Gingras M, Farand P, Safar ME, Plante GE. 2009. Adventitia: the vital wall of conduit arteries. J. Am. Soc. Hypertens. 3:166–83
    [Google Scholar]
  38. 38. 
    Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. 2002. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol. 3:349–63
    [Google Scholar]
  39. 39. 
    Hinz B. 2010. The myofibroblast: paradigm for a mechanically active cell. J. Biomech. 43:146–55
    [Google Scholar]
  40. 40. 
    Heegaard AM, Corsi A, Danielsen CC, Nielsen KL, Jorgensen HL et al. 2007. Biglycan deficiency causes spontaneous aortic dissection and rupture in mice. Circulation 115:2731–38
    [Google Scholar]
  41. 41. 
    Meester JA, Vandeweyer G, Pintelon I, Lammens M, Van Hoorick L et al. 2017. Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections. Genet. Med. 19:386–95
    [Google Scholar]
  42. 42. 
    Chiquet M, Gelman L, Lutz R, Maier S. 2009. From mechanotransduction to extracellular matrix gene expression in fibroblasts. Biochim. Biophys. Acta 1793:911–20
    [Google Scholar]
  43. 43. 
    Janmey PA, Wells RG, Assoian RK, McCulloch CA. 2013. From tissue mechanics to transcription factors. Differentiation 86:112–20
    [Google Scholar]
  44. 44. 
    Herum KM, Lunde IG, McCulloch AD, Christensen G. 2017. The soft- and hard-heartedness of cardiac fibroblasts: mechanotransduction signaling pathways in fibrosis of the heart. J. Clin. Med. 6:53
    [Google Scholar]
  45. 45. 
    Wu J, Thabet SR, Kirabo A, Trott DW, Saleh MA et al. 2014. Inflammation and mechanical stretch promote aortic stiffening in hypertension through activation of p38 mitogen-activated protein kinase. Circ. Res. 114:616–25
    [Google Scholar]
  46. 46. 
    Saini K, Cho S, Dooling LJ, Discher DE. 2020. Tension in fibrils suppresses their enzymatic degradation: a molecular mechanism for “use it or lose it.”. Matrix Biol 85–86:34–46
    [Google Scholar]
  47. 47. 
    Wagenseil JE, Mecham RP. 2009. Vascular extracellular matrix and arterial mechanics. Physiol. Rev. 89:957–89
    [Google Scholar]
  48. 48. 
    Humphries JD, Chastney MR, Askari JA, Humphries MJ. 2019. Signal transduction via integrin adhesion complexes. Curr. Opin. Cell Biol. 56:14–21
    [Google Scholar]
  49. 49. 
    Finney AC, Stokes KY, Pattillo CB, Orr AW. 2017. Integrin signaling in atherosclerosis. Cell. Mol. Life Sci. 74:2263–82
    [Google Scholar]
  50. 50. 
    Schultz GS, Wysocki A. 2009. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 17:153–62
    [Google Scholar]
  51. 51. 
    Hinz B. 2015. The extracellular matrix and transforming growth factor-β1: tale of a strained relationship. Matrix Biol 47:54–65
    [Google Scholar]
  52. 52. 
    Tremble P, Damsky CH, Werb Z. 1995. Components of the nuclear signaling cascade that regulate collagenase gene expression in response to integrin-derived signals. J. Cell Biol. 129:1707–20
    [Google Scholar]
  53. 53. 
    Gomez D, Owens GK. 2012. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc. Res. 95:156–64
    [Google Scholar]
  54. 54. 
    Davis GE. 1992. Affinity of integrins for damaged extracellular matrix: αvβ3 binds to denatured collagen type I through RGD sites. Biochem. Biophys. Res. Commun. 182:1025–31
    [Google Scholar]
  55. 55. 
    Xu J, Rodriguez D, Petitclerc E, Kim JJ, Hangai M et al. 2001. Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. J. Cell Biol. 154:1069–79
    [Google Scholar]
  56. 56. 
    Wells JM, Gaggar A, Blalock JE. 2015. MMP generated matrikines. Matrix Biol 44–46:122–29
    [Google Scholar]
  57. 57. 
    Ortega N, Werb Z. 2002. New functional roles for non-collagenous domains of basement membrane collagens. J. Cell Sci. 115:4201–14
    [Google Scholar]
  58. 58. 
    Cannon WB. 1929. Organization for physiological homeostasis. Physiol. Rev. 9:399–431
    [Google Scholar]
  59. 59. 
    Humphrey JD. 2008. Vascular adaptation and mechanical homeostasis at tissue, cellular, and sub-cellular levels. Cell Biochem. Biophys. 50:53–78
    [Google Scholar]
  60. 60. 
    Matsumoto T, Hayashi K. 1994. Mechanical and dimensional adaptation of rat aorta to hypertension. J. Biomech. Eng. 116:278–83
    [Google Scholar]
  61. 61. 
    Wolinsky H, Glagov S. 1967. A lamellar unit of aortic medial structure and function in mammals. Circ. Res. 20:99–111
    [Google Scholar]
  62. 62. 
    Intengan HD, Schiffrin EL. 2001. Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension 38:581–87
    [Google Scholar]
  63. 63. 
    Laurent S, Boutouyrie P. 2015. The structural factor of hypertension: large and small artery alterations. Circ. Res. 116:1007–21
    [Google Scholar]
  64. 64. 
    Martinez-Lemus LA, Hill MA, Meininger GA. 2009. The plastic nature of the vascular wall: a continuum of remodeling events contributing to control of arteriolar diameter and structure. Physiology 24:45–57
    [Google Scholar]
  65. 65. 
    Marenzana M, Wilson-Jones N, Mudera V, Brown RA 2006. The origins and regulation of tissue tension: identification of collagen tension-fixation process in vitro. Exp. Cell Res. 312:423–33
    [Google Scholar]
  66. 66. 
    Brown RA, Prajapati R, McGrouther DA, Yannas IV, Eastwood M. 1998. Tensional homeostasis in dermal fibroblasts: mechanical responses to mechanical loading in three-dimensional substrates. J. Cell Physiol. 175:323–32
    [Google Scholar]
  67. 67. 
    Mizutani T, Haga H, Kawabata K. 2004. Cellular stiffness response to external deformation: tensional homeostasis in a single fibroblast. Cell Motil. Cytoskelet. 59:242–48
    [Google Scholar]
  68. 68. 
    Rudic RD, Shesely EG, Maeda N, Smithies O, Segal SS, Sessa WC. 1998. Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J. Clin. Investig. 101:731–36
    [Google Scholar]
  69. 69. 
    Burton AC. 1954. Relation of structure to function of the tissues of the wall of blood vessels. Physiol. Rev. 34:619–42
    [Google Scholar]
  70. 70. 
    Bellini C, Ferruzzi J, Roccabianca S, Di Martino ES, Humphrey JD. 2014. A microstructurally motivated model of arterial wall mechanics with mechanobiological implications. Ann. Biomed. Eng. 42:488–502
    [Google Scholar]
  71. 71. 
    Schwartz MA, Vestweber D, Simons M. 2018. A unifying concept in vascular health and disease. Science 360:270–71
    [Google Scholar]
  72. 72. 
    Valentin A, Humphrey JD. 2009. Evaluation of fundamental hypotheses underlying constrained mixture models of arterial growth and remodelling. Philos. Trans. A Math. Phys. Eng. Sci. 367:3585–606
    [Google Scholar]
  73. 73. 
    Latorre M, Humphrey JD. 2019. Mechanobiological stability of biological soft tissues. J. Mech. Phys. Solids 125:298–325
    [Google Scholar]
  74. 74. 
    Nissen R, Cardinale GJ, Udenfriend S 1978. Increased turnover of arterial collagen in hypertensive rats. PNAS 75:451–53
    [Google Scholar]
  75. 75. 
    Taber LA. 1998. A model for aortic growth based on fluid shear and fiber stresses. J. Biomech. Eng. 120:348–54
    [Google Scholar]
  76. 76. 
    Ambrosi D, Ben Amar M, Cyron CJ, DeSimone A, Goriely A et al. 2019. Growth and remodelling of living tissues: perspectives, challenges and opportunities. J. R. Soc. Interface 16:20190233
    [Google Scholar]
  77. 77. 
    Myers PR, Tanner MA. 1998. Vascular endothelial cell regulation of extracellular matrix collagen: role of nitric oxide. Arterioscler. Thromb. Vasc. Biol. 18:717–22
    [Google Scholar]
  78. 78. 
    Shi-Wen X, Renzoni EA, Kennedy L, Howat S, Chen Y et al. 2007. Endogenous endothelin-1 signaling contributes to type I collagen and CCN2 overexpression in fibrotic fibroblasts. Matrix Biol 26:625–32
    [Google Scholar]
  79. 79. 
    Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C et al. 2006. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur. Heart J. 27:2588–605
    [Google Scholar]
  80. 80. 
    Demiray H. 1992. Wave propagation through a viscous fluid contained in a prestressed thin elastic tube. Int. J. Eng. Sci. 30:1607–20
    [Google Scholar]
  81. 81. 
    Humphrey JD, Harrison DG, Figueroa CA, Lacolley P, Laurent S 2016. Central artery stiffness in hypertension and aging: a problem with cause and consequence. Circ. Res. 118:379–81
    [Google Scholar]
  82. 82. 
    Dampney RAL. 2017. Resetting of the baroreflex control of sympathetic vasomotor activity during natural behaviors: description and conceptual model of central mechanisms. Front. Neurosci. 11:461
    [Google Scholar]
  83. 83. 
    Cai H, Harrison DG. 2000. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ. Res. 87:840–44
    [Google Scholar]
  84. 84. 
    Davignon J, Ganz P. 2004. Role of endothelial dysfunction in atherosclerosis. Circulation 109:III27–32
    [Google Scholar]
  85. 85. 
    Endemann DH, Schiffrin EL. 2004. Endothelial dysfunction. J. Am. Soc. Nephrol. 15:1983–92
    [Google Scholar]
  86. 86. 
    Virdis A, Schiffrin EL. 2003. Vascular inflammation: a role in vascular disease in hypertension?. Curr. Opin. Nephrol. Hypertens. 12:181–87
    [Google Scholar]
  87. 87. 
    Harrison DG, Widder J, Grumbach I, Chen W, Weber M, Searles C. 2006. Endothelial mechanotransduction, nitric oxide and vascular inflammation. J. Intern. Med. 259:351–63
    [Google Scholar]
  88. 88. 
    Sprague AH, Khalil RA. 2009. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem. Pharmacol. 78:539–52
    [Google Scholar]
  89. 89. 
    Szmitko PE, Wang CH, Weisel RD, Jeffries GA, Anderson TJ, Verma S. 2003. Biomarkers of vascular disease linking inflammation to endothelial activation. Part II. Circulation 108:2041–48
    [Google Scholar]
  90. 90. 
    Csiszar A, Wang M, Lakatta EG, Ungvari Z. 2008. Inflammation and endothelial dysfunction during aging: role of NF-κB. J. Appl. Physiol. 105:1333–41
    [Google Scholar]
  91. 91. 
    Harvey A, Montezano AC, Lopes RA, Rios F, Touyz RM. 2016. Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications. Can. J. Cardiol. 32:659–68
    [Google Scholar]
  92. 92. 
    Latorre M, Bersi MR, Humphrey JD 2019. Computational modeling predicts immuno-mechanical mechanisms of maladaptive aortic remodeling in hypertension. Int. J. Eng. Sci. 151:35–46
    [Google Scholar]
  93. 93. 
    Wang M, Zhang J, Jiang LQ, Spinetti G, Pintus G et al. 2007. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension 50:219–27
    [Google Scholar]
  94. 94. 
    Tellides G, Pober JS. 2015. Inflammatory and immune responses in the arterial media. Circ. Res. 116:312–22
    [Google Scholar]
  95. 95. 
    Choke E, Cockerill G, Wilson WR, Sayed S, Dawson J et al. 2005. A review of biological factors implicated in abdominal aortic aneurysm rupture. Eur. J. Vasc. Endovasc. Surg. 30:227–44
    [Google Scholar]
  96. 96. 
    Szasz T, Bomfim GF, Webb RC 2013. The influence of perivascular adipose tissue on vascular homeostasis. Vasc. Health Risk Manag 9:105–16
    [Google Scholar]
  97. 97. 
    Lee HY, Despres JP, Koh KK. 2013. Perivascular adipose tissue in the pathogenesis of cardiovascular disease. Atherosclerosis 230:177–84
    [Google Scholar]
  98. 98. 
    Medzhitov R. 2008. Origin and physiological roles of inflammation. Nature 454:428–35
    [Google Scholar]
  99. 99. 
    Kotas ME, Medzhitov R. 2015. Homeostasis, inflammation, and disease susceptibility. Cell 160:816–27
    [Google Scholar]
  100. 100. 
    Mrosovsky N. 1990. Rheostasis: The Physiology of Change New York, NY/Oxford, UK: Oxford Univ. Press
  101. 101. 
    Davies KJ. 2016. Adaptive homeostasis. Mol. Aspects Med. 49:1–7
    [Google Scholar]
  102. 102. 
    Ley K. 1996. Molecular mechanisms of leukocyte recruitment in the inflammatory process. Cardiovasc. Res. 32:733–42
    [Google Scholar]
  103. 103. 
    Kreuger J, Phillipson M. 2016. Targeting vascular and leukocyte communication in angiogenesis, inflammation and fibrosis. Nat. Rev. Drug Discov. 15:125–42
    [Google Scholar]
  104. 104. 
    Chen JY, Ye ZX, Wang XF, Chang J, Yang MW et al. 2018. Nitric oxide bioavailability dysfunction involves in atherosclerosis. Biomed. Pharmacother. 97:423–28
    [Google Scholar]
  105. 105. 
    Pacher P, Beckman JS, Liaudet L. 2007. Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 87:315–424
    [Google Scholar]
  106. 106. 
    Bersi MR, Khosravi R, Wujciak AJ, Harrison DG, Humphrey JD. 2017. Differential cell-matrix mechanoadaptations and inflammation drive regional propensities to aortic fibrosis, aneurysm or dissection in hypertension. J. R. Soc. Interface 14:20170327
    [Google Scholar]
  107. 107. 
    Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. 1996. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J. Clin. Investig. 98:2572–79
    [Google Scholar]
  108. 108. 
    Touyz RM. 2005. Molecular and cellular mechanisms in vascular injury in hypertension: role of angiotensin II. Curr. Opin. Nephrol. Hypertens. 14:125–31
    [Google Scholar]
  109. 109. 
    Lacolley P, Safar ME, Regnault V, Frohlich ED. 2009. Angiotensin II, mechanotransduction, and pulsatile arterial hemodynamics in hypertension. Am. J. Physiol. Heart Circ. Physiol. 297:H1567–75
    [Google Scholar]
  110. 110. 
    Tieu BC, Ju X, Lee C, Sun H, Lejeune W et al. 2011. Aortic adventitial fibroblasts participate in angiotensin-induced vascular wall inflammation and remodeling. J. Vasc. Res. 48:261–72
    [Google Scholar]
  111. 111. 
    Poduri A, Owens AP 3rd, Howatt DA, Moorleghen JJ, Balakrishnan A et al. 2012. Regional variation in aortic AT1b receptor mRNA abundance is associated with contractility but unrelated to atherosclerosis and aortic aneurysms. PLOS ONE 7:e48462
    [Google Scholar]
  112. 112. 
    Gallardo-Ortíz IA, Rodríguez-Hernández SN, López-Guerrero JJ, Del Valle–Mondragón L, López-Sánchez P et al. 2015. Role of α1D-adrenoceptors in vascular wall hypertrophy during angiotensin II–induced hypertension. Auton. Autacoid Pharmacol. 35:17–31
    [Google Scholar]
  113. 113. 
    Trachet B, Renard M, De Santis G, Staelens S, De Backer J et al. 2011. An integrated framework to quantitatively link mouse-specific hemodynamics to aneurysm formation in angiotensin II–infused ApoE−/− mice. Ann. Biomed. Eng. 39:2430–44
    [Google Scholar]
  114. 114. 
    Hibino N, Yi T, Duncan DR, Rathore A, Dean E et al. 2011. A critical role for macrophages in neovessel formation and the development of stenosis in tissue-engineered vascular grafts. FASEB J 25:4253–63
    [Google Scholar]
  115. 115. 
    Khosravi R, Miller KS, Best CA, Shih YC, Lee YU et al. 2015. Biomechanical diversity despite mechanobiological stability in tissue engineered vascular grafts two years post-implantation. Tissue Eng. A 21:1529–38
    [Google Scholar]
  116. 116. 
    Kelleher CM, McLean SE, Mecham RP. 2004. Vascular extracellular matrix and aortic development. Curr. Top. Dev. Biol. 62:153–88
    [Google Scholar]
  117. 117. 
    Parker MW, Rossi D, Peterson M, Smith K, Sikstrom K et al. 2014. Fibrotic extracellular matrix activates a profibrotic positive feedback loop. J. Clin. Investig. 124:1622–35
    [Google Scholar]
  118. 118. 
    Marinkovic A, Liu F, Tschumperlin DJ. 2013. Matrices of physiologic stiffness potently inactivate idiopathic pulmonary fibrosis fibroblasts. Am. J. Respir. Cell Mol. Biol. 48:422–30
    [Google Scholar]
  119. 119. 
    Hoffman BD, Grashoff C, Schwartz MA. 2011. Dynamic molecular processes mediate cellular mechanotransduction. Nature 475:316–23
    [Google Scholar]
  120. 120. 
    Janmey PA, Fletcher DA, Reinhart-King CA. 2020. Stiffness sensing by cells. Physiol. Rev. 100:695–724
    [Google Scholar]
  121. 121. 
    Georges PC, Janmey PA. 2005. Cell type–specific response to growth on soft materials. J. Appl. Physiol. 98:1547–53
    [Google Scholar]
  122. 122. 
    Sabine A, Bovay E, Demir CS, Kimura W, Jaquet M et al. 2015. FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature. J. Clin. Investig. 125:3861–77
    [Google Scholar]
  123. 123. 
    Souilhol C, Harmsen MC, Evans PC, Krenning G. 2018. Endothelial-mesenchymal transition in atherosclerosis. Cardiovasc. Res. 114:565–77
    [Google Scholar]
  124. 124. 
    Chen PY, Qin L, Li G, Wang Z, Dahlman JE et al. 2019. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nat. Metab. 1:912–26
    [Google Scholar]
  125. 125. 
    Shankman LS, Gomez D, Cherepanova OA, Salmon M, Alencar GF et al. 2015. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat. Med. 21:628–37
    [Google Scholar]
  126. 126. 
    Alencar GF, Owsiany KM, Karnewar S, Sukhavasi K, Mocci G et al. 2020. Stem cell pluripotency genes Klf4 and Oct4 regulate complex SMC phenotypic changes critical in late-stage atherosclerotic lesion pathogenesis. Circulation 142:2045–59
    [Google Scholar]
  127. 127. 
    Humphrey JD, Taylor CA. 2008. Intracranial and abdominal aortic aneurysms: similarities, differences, and need for a new class of computational models. Annu. Rev. Biomed. Eng. 10:221–46
    [Google Scholar]
  128. 128. 
    Humphrey JD, Holzapfel GA. 2012. Mechanics, mechanobiology, and modeling of human abdominal aorta and aneurysms. J. Biomech. 45:805–14
    [Google Scholar]
  129. 129. 
    Sakalihasan N, Limet R, Defawe OD. 2005. Abdominal aortic aneurysm. Lancet 365:1577–89
    [Google Scholar]
  130. 130. 
    Boussel L, Rayz V, McCulloch C, Martin A, Acevedo-Bolton G et al. 2008. Aneurysm growth occurs at region of low wall shear stress: patient-specific correlation of hemodynamics and growth in a longitudinal study. Stroke 39:2997–3002
    [Google Scholar]
  131. 131. 
    Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. 2015. Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections. Circ. Res. 116:1448–61
    [Google Scholar]
  132. 132. 
    Milewicz DM, Trybus KM, Guo DC, Sweeney HL, Regalado E et al. 2017. Altered smooth muscle cell force generation as a driver of thoracic aortic aneurysms and dissections. Arterioscler. Thromb. Vasc. Biol. 37:26–34
    [Google Scholar]
  133. 133. 
    Chen PY, Qin L, Li G, Malagon-Lopez J, Wang Z et al. 2020. Smooth muscle cell reprogramming in aortic aneurysms. Cell Stem Cell 26:542–57.e11
    [Google Scholar]
  134. 134. 
    Li G, Wang M, Caulk AW, Cilfone NA, Gujja S et al. 2020. Chronic mTOR activation induces a degradative smooth muscle cell phenotype. J. Clin. Investig. 130:1233–51
    [Google Scholar]
  135. 135. 
    Libby P. 2002. Inflammation in atherosclerosis. Nature 420:868–74
    [Google Scholar]
  136. 136. 
    Hahn C, Schwartz MA. 2009. Mechanotransduction in vascular physiology and atherogenesis. Nat. Rev. Mol. Cell Biol. 10:53–62
    [Google Scholar]
  137. 137. 
    Ku DN, Giddens DP, Zarins CK, Glagov S. 1985. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 5:293–302
    [Google Scholar]
  138. 138. 
    Chiu JJ, Chien S. 2011. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol. Rev. 91:327–87
    [Google Scholar]
  139. 139. 
    Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA et al. 2005. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437:426–31
    [Google Scholar]
  140. 140. 
    David G, Humphrey JD. 2003. Further evidence for the dynamic stability of intracranial saccular aneurysms. J. Biomech. 36:1143–50
    [Google Scholar]
  141. 141. 
    Cyron CJ, Wilson JS, Humphrey JD. 2014. Mechanobiological stability: a new paradigm to understand the enlargement of aneurysms?. J. R. Soc. Interface 11:20140680
    [Google Scholar]
  142. 142. 
    Cyron CJ, Humphrey JD. 2014. Vascular homeostasis and the concept of mechanobiological stability. Int. J. Eng. Sci. 85:203–23
    [Google Scholar]
  143. 143. 
    Maegdefessel L, Azuma J, Toh R, Merk DR, Deng A et al. 2012. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J. Clin. Investig. 122:497–506
    [Google Scholar]
  144. 144. 
    Wilson JS, Baek S, Humphrey JD. 2013. Parametric study of effects of collagen turnover on the natural history of abdominal aortic aneurysms. Proc. Math. Phys. Eng. Sci. 469:20120556
    [Google Scholar]
  145. 145. 
    Satha G, Lindstrom SB, Klarbring A. 2014. A goal function approach to remodeling of arteries uncovers mechanisms for growth instability. Biomech. Model. Mechanobiol. 13:1243–59
    [Google Scholar]
  146. 146. 
    Erlich A, Moulton DE, Goriely A. 2019. Are homeostatic states stable? Dynamical stability in morpho-elasticity. Bull. Math. Biol. 81:3219–44
    [Google Scholar]
  147. 147. 
    Bu DX, Tarrio M, Grabie N, Zhang Y, Yamazaki H et al. 2010. Statin-induced Krüppel-like factor 2 expression in human and mouse T cells reduces inflammatory and pathogenic responses. J. Clin. Investig. 120:1961–70
    [Google Scholar]
  148. 148. 
    Sen-Banerjee S, Mir S, Lin Z, Hamik A, Atkins GB et al. 2005. Krüppel-like factor 2 as a novel mediator of statin effects in endothelial cells. Circulation 112:720–26
    [Google Scholar]
  149. 149. 
    Brasier AR, Recinos A 3rd, Eledrisi MS 2002. Vascular inflammation and the renin-angiotensin system. Arterioscler. Thromb. Vasc. Biol. 22:1257–66
    [Google Scholar]
  150. 150. 
    Wong CH, Siah KW, Lo AW. 2019. Estimation of clinical trial success rates and related parameters. Biostatistics 20:273–86
    [Google Scholar]
  151. 151. 
    Takebe T, Imai R, Ono S. 2018. The current status of drug discovery and development as originated in United States academia: the influence of industrial and academic collaboration on drug discovery and development. Clin. Transl. Sci. 11:597–606
    [Google Scholar]
  152. 152. 
    Saucerman JJ, Tan PM, Buchholz KS, McCulloch AD, Omens JH. 2019. Mechanical regulation of gene expression in cardiac myocytes and fibroblasts. Nat. Rev. Cardiol. 16:361–78
    [Google Scholar]
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