1932

Abstract

Mechanical forces influence different cell types in our bodies. Among the earliest forces experienced in mammals is blood movement in the vascular system. Blood flow starts at the embryonic stage and ceases when the heart stops. Blood flow exposes endothelial cells (ECs) that line all blood vessels to hemodynamic forces. ECs detect these mechanical forces (mechanosensing) through mechanosensors, thus triggering physiological responses such as changes in vascular diameter. In this review, we focus on endothelial mechanosensing and on how different ion channels, receptors, and membrane structures detect forces and mediate intricate mechanotransduction responses. We further highlight that these responses often reflect collaborative efforts involving several mechanosensors and mechanotransducers. We close with a consideration of current knowledge regarding the dysregulation of endothelial mechanosensing during disease. Because hemodynamic disruptions are hallmarks of cardiovascular disease, studying endothelial mechanosensing holds great promise for advancing our understanding of vascular physiology and pathophysiology.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-042022-030946
2024-02-12
2024-05-05
Loading full text...

Full text loading...

/deliver/fulltext/physiol/86/1/annurev-physiol-042022-030946.html?itemId=/content/journals/10.1146/annurev-physiol-042022-030946&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Abraira VE, Ginty DD. 2013. The sensory neurons of touch. Neuron 79:4618–39
    [Google Scholar]
  2. 2.
    Hahn C, Schwartz MA. 2009. Mechanotransduction in vascular physiology and atherogenesis. Nat. Rev. 10:153–62
    [Google Scholar]
  3. 3.
    Cecchi E, Giglioli C, Valente S, Lazzeri C, Gensini GF et al. 2011. Role of hemodynamic shear stress in cardiovascular disease. Atherosclerosis 214:2249–56
    [Google Scholar]
  4. 4.
    Kubota Y, Kleinman HK, Martin GR, Lawley TJ. 1988. Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures. J. Cell Biol. 107:41589–98
    [Google Scholar]
  5. 5.
    Przysinda A, Feng W, Li G. 2020. Diversity of organism-wide and organ-specific endothelial cells. Curr. Cardiol. Rep. 22:19
    [Google Scholar]
  6. 6.
    Eelen G, de Zeeuw P, Treps L, Harjes U, Wong BW, Carmeliet P. 2018. Endothelial cell metabolism. Physiol. Rev. 98:13–58
    [Google Scholar]
  7. 7.
    Dalal PJ, Muller WA, Sullivan DP. 2020. Endothelial cell calcium signaling during barrier function and inflammation. Am. J. Pathol. 190:3535–42
    [Google Scholar]
  8. 8.
    Paszkowiak JJ, Dardik A, Haven N. 2003. Basic science review arterial wall shear stress: observations from the bench to the bedside. Vasc. Endovasc. Surg. 37:147–57
    [Google Scholar]
  9. 9.
    Belloni FL. 1999. Teaching the principles of hemodynamics. Adv. Physiol. Educ. 277:6S187–202
    [Google Scholar]
  10. 10.
    Langille B. 1993. Remodeling of developing and mature arteries: endothelium, smooth muscle, and matrix. J. Cardiovasc. Pharmacol. 21:S11–17
    [Google Scholar]
  11. 11.
    Badeer HS. 2001. Hemodynamics for medical students. Adv. Physiol. Educ. 25:144–52
    [Google Scholar]
  12. 12.
    Pyke KE, Tschakovsky ME. 2005. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function. J. Physiol. 568:Part 2357–69
    [Google Scholar]
  13. 13.
    Davies PF. 1995. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75:3519–60
    [Google Scholar]
  14. 14.
    Drew PJ. 2022. Neurovascular coupling: motive unknown. Trends Neurosci. 45:11809–19
    [Google Scholar]
  15. 15.
    Godo S, Shimokawa H. 2017. Endothelial functions. Arterioscler. Thromb. Vasc. Biol. 37:9e108–14
    [Google Scholar]
  16. 16.
    Ando J, Yamamoto K. 2009. Vascular mechanobiology endothelial cell responses to fluid shear stress. Circ. J. 73:1983–92
    [Google Scholar]
  17. 17.
    Li J, Hou B, Tumova S, Muraki K, Bruns A et al. 2014. Piezo1 integration of vascular architecture with physiological force. Nature 515:7526279–82
    [Google Scholar]
  18. 18.
    Malek AM, Alper SL, Izumo S. 1999. Hemodynamic shear stress and its role in atherosclerosis. JAMA 282:212035–42
    [Google Scholar]
  19. 19.
    Dewey CF, Bussolari SR, Gimbrone MA, Davies PF. 1981. The dynamic response of vascular endothelial cells to fluid shear stress. J. Biomech. Eng. 103:3177–85
    [Google Scholar]
  20. 20.
    Fang Y, Wu D, Birukov KG. 2019. Mechanosensing and mechanoregulation of endothelial cell functions. Compr. Physiol. 9:2873–904
    [Google Scholar]
  21. 21.
    Davis MJ, Earley S, Li Y-S, Chien S. 2023. Vascular mechanotransduction. Physiol. Rev. 103:21247–421
    [Google Scholar]
  22. 22.
    Lansman JB, Hallam TJ, Rink TJ. 1987. Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers?. Nature 325:6107811–13
    [Google Scholar]
  23. 23.
    Olesen S-P, Clapham D, Davies PF 1988. Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331:6152168–70
    [Google Scholar]
  24. 24.
    Árnadóttir J, Chalfie M. 2010. Eukaryotic mechanosensitive channels. Annu. Rev. Biophys. 39:111–37
    [Google Scholar]
  25. 25.
    Syeda R, Florendo MN, Cox CD, Kefauver JM, Santos JS et al. 2016. Piezo1 channels are inherently mechanosensitive. Cell Rep. 17:71739–46
    [Google Scholar]
  26. 26.
    Harraz OF, Klug NR, Senatore AJ, Hill-Eubanks DC, Nelson MT. 2022. Piezo1 is a mechanosensor channel in central nervous system capillaries. Circ. Res. 130:101531–46
    [Google Scholar]
  27. 27.
    Wang SP, Chennupati R, Kaur H, Iring A, Wettschureck N, Offermanns S. 2016. Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J. Clin. Investig. 126:124527–36
    [Google Scholar]
  28. 28.
    Ranade SS, Qiu Z, Woo SH, Hur SS, Murthy SE et al. 2014. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. PNAS 111:2810347–52
    [Google Scholar]
  29. 29.
    Kang H, Hong Z, Zhong M, Klomp J, Bayless KJ et al. 2019. Piezo1 mediates angiogenesis through activation of MT1-MMP signaling. Am. J. Physiol. Cell Physiol. 316:1C92–103
    [Google Scholar]
  30. 30.
    Liu T, Du X, Zhang B, Zi H, Yan Y et al. 2020. Piezo1-mediated Ca2+ activities regulate brain vascular pathfinding during development. Neuron 108:1180–192.e5
    [Google Scholar]
  31. 31.
    Rode B, Shi J, Endesh N, Drinkhill MJ, Webster PJ et al. 2017. Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance. Nat. Commun. 8:1350
    [Google Scholar]
  32. 32.
    Lhomme A, Gilbert G, Pele T, Deweirdt J, Henrion D et al. 2019. Stretch-activated Piezo1 channel in endothelial cells relaxes mouse intrapulmonary arteries. Am. J. Respir. Cell Mol. Biol. 60:6650–58
    [Google Scholar]
  33. 33.
    John L, Ko NL, Gokin A, Gokina N, Mandalà M, Osol G. 2018. The Piezo1 cation channel mediates uterine artery shear stress mechanotransduction and vasodilation during rat pregnancy. Am. J. Physiol. Heart Circ. Physiol. 315:4H1019–26
    [Google Scholar]
  34. 34.
    Evans EL, Cuthbertson K, Endesh N, Rode B, Blythe NM et al. 2018. Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation. Br. J. Pharmacol. 175:101744–59
    [Google Scholar]
  35. 35.
    Albarrán-Juárez J, Iring A, Wang S, Joseph S, Grimm M et al. 2018. Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation. J. Exp. Med. 215:102655–72
    [Google Scholar]
  36. 36.
    Harraz OF, Longden TA, Hill-Eubanks D, Nelson MT. 2018. PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells. eLife 7:e38689
    [Google Scholar]
  37. 37.
    Harraz OF, Longden TA, Dabertrand F, Hill-Eubanks D, Nelson MT. 2018. Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIP2 depletion. PNAS 115:15E3569–77
    [Google Scholar]
  38. 38.
    Ye Y, Barghouth M, Dou H, Luan C, Wang Y et al. 2022. A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells. Nat. Commun. 13:4237
    [Google Scholar]
  39. 39.
    Wu D, Minami M, Kawamura H, Puro D. 2006. Electrotonic transmission within pericyte-containing retinal microvessels. Microcirculation 13:5353–63
    [Google Scholar]
  40. 40.
    Yamamoto Y, Imaeda K, Suzuki H. 1999. Endothelium-dependent hyperpolarization and intercellular electrical coupling in guinea-pig mesenteric arterioles. J. Physiol. 514:Part 2505–13
    [Google Scholar]
  41. 41.
    Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B. 2002. Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J. Biol. Chem. 277:4947044–51
    [Google Scholar]
  42. 42.
    Köhler R, Heyken W-T, Heinau P, Schubert R, Si H et al. 2006. Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation. Arterioscler. Thromb. Vasc. Biol. 26:71495–502
    [Google Scholar]
  43. 43.
    Hartmannsgruber V, Heyken WT, Kacik M, Kaistha A, Grgic I et al. 2007. Arterial response to shear stress critically depends on endothelial TRPV4 expression. PLOS ONE 2:9e827
    [Google Scholar]
  44. 44.
    Mendoza SA, Fang J, Gutterman DD, Wilcox DA, Bubolz AH et al. 2010. TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress. Am. J. Physiol. Heart Circ. Physiol. 298:466–76
    [Google Scholar]
  45. 45.
    Earley S, Brayden JE. 2015. Transient receptor channels in the vasculature. Physiol. Rev. 95:645–90
    [Google Scholar]
  46. 46.
    Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD. 2000. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol. 2:10695–702
    [Google Scholar]
  47. 47.
    Liedtke W, Choe Y, Martí-Renom MA, Bell AM, Denis CS et al. 2000. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103:3525–35
    [Google Scholar]
  48. 48.
    White JPM, Cibelli M, Urban L, Nilius B, McGeown JG, Nagy I. 2016. TRPV4: molecular conductor of a diverse orchestra. Physiol. Rev. 96:3911–73
    [Google Scholar]
  49. 49.
    Loukin S, Zhou X, Su Z, Saimi Y, Kung C. 2010. Wild-type and brachyolmia-causing mutant TRPV4 channels respond directly to stretch force. J. Biol. Chem. 285:3527176–81
    [Google Scholar]
  50. 50.
    Servin-Vences MR, Moroni M, Lewin GR, Poole K. 2017. Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. eLife 6:e21074
    [Google Scholar]
  51. 51.
    Nikolaev YA, Cox CD, Ridone P, Rohde PR, Cordero-Morales JF et al. 2019. Mammalian TRP ion channels are insensitive to membrane stretch. J. Cell Sci. 132:jcs238360
    [Google Scholar]
  52. 52.
    Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nillus B. 2003. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:6947434–38
    [Google Scholar]
  53. 53.
    Loot AE, Popp R, Fisslthaler B, Vriens J, Nilius B, Fleming I. 2008. Role of cytochrome P450-dependent transient receptor potential V4 activation in flow-induced vasodilatation. Cardiovasc. Res. 80:3445–52
    [Google Scholar]
  54. 54.
    Swain SM, Liddle RA. 2021. Piezo1 acts upstream of TRPV4 to induce pathological changes in endothelial cells due to shear stress. J. Biol. Chem. 296:100171
    [Google Scholar]
  55. 55.
    Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotlikoff MI et al. 2012. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science 336:6081597–601
    [Google Scholar]
  56. 56.
    Longden TA, Mughal A, Hennig GW, Harraz OF, Shui B et al. 2021. Local IP3 receptor-mediated Ca2+ signals compound to direct blood flow in brain capillaries. Sci. Adv. 7:30eabh0101
    [Google Scholar]
  57. 57.
    McFarland SJ, Weber DS, Choi C-S, Lin MT, Taylor MS. 2020. Ablation of endothelial TRPV4 channels alters the dynamic Ca2+ signaling profile in mouse carotid arteries. Int. J. Mol. Sci. 21:62179
    [Google Scholar]
  58. 58.
    Heathcote HR, Lee MD, Zhang X, Saunter CD, Wilson C, McCarron JG. 2019. Endothelial TRPV4 channels modulate vascular tone by Ca2+-induced Ca2+ release at inositol 1,4,5-trisphosphate receptors. Br. J. Pharmacol. 176:173297–317
    [Google Scholar]
  59. 59.
    Sonkusare SK, Dalsgaard T, Bonev AD, Hill-Eubanks DC, Kotlikoff MI et al. 2014. AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension. Sci. Signal. 7:333ra66
    [Google Scholar]
  60. 60.
    Xu J, Mathur J, Vessières E, Hammack S, Nonomura K et al. 2018. GPR68 senses flow and is essential for vascular physiology. Cell 173:3762–75.e16
    [Google Scholar]
  61. 61.
    Rath G, Saliez J, Behets G, Romero-Perez M, Leon-Gomez E et al. 2012. Vascular hypoxic preconditioning relies on TRPV4-dependent calcium influx and proper intercellular gap junctions communication. Arterioscler. Thromb. Vasc. Biol. 32:92241–49
    [Google Scholar]
  62. 62.
    Saliez J, Bouzin C, Rath G, Ghisdal P, Desjardins F et al. 2008. Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation. Circulation 117:81065–74
    [Google Scholar]
  63. 63.
    Thakore P, Alvarado MG, Ali S, Mughal A, Pires PW et al. 2021. Brain endothelial cell TRPA1 channels initiate neurovascular coupling. eLife 10:e63040
    [Google Scholar]
  64. 64.
    Sullivan MN, Gonzales A, Pires PW, Leo MD, Gonzales AL et al. 2015. Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation. Sci. Signal. 8:358ra2
    [Google Scholar]
  65. 65.
    Longden TA, Dabertrand F, Koide M, Gonzales AL, Tykocki NR et al. 2017. Capillary K+-sensing initiates retrograde hyperpolarization to locally increase cerebral blood flow. Nat. Neurosci. 20:717–26
    [Google Scholar]
  66. 66.
    Ahn SJ, Fancher IS, Bian JT, Zhang CX, Schwab S et al. 2017. Inwardly rectifying K+ channels are major contributors to flow-induced vasodilatation in resistance arteries. J. Physiol. 595:72339–64
    [Google Scholar]
  67. 67.
    Zaritsky JJ, Eckman DM, Wellman GC, Nelson MT, Schwarz TL. 2000. Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K+ current in K+-mediated vasodilation. Circ. Res. 87:2160–66
    [Google Scholar]
  68. 68.
    Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. 2010. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol. Rev. 90:1291–366
    [Google Scholar]
  69. 69.
    Hoger JH, Ilyin VI, Forsyth S, Hoger A. 2002. Shear stress regulates the endothelial Kir2.1 ion channel. PNAS 99:117780–85
    [Google Scholar]
  70. 70.
    Lieu DK, Pappone PA, Barakat AI. 2004. Differential membrane potential and ion current responses to different types of shear stress in vascular endothelial cells. Am. J. Physiol. Cell Physiol. 286:61367–75
    [Google Scholar]
  71. 71.
    Jacobs ER, Cheliakine C, Gebremedhin D, Birks EK, Davies PF, Harder DR. 1995. Shear activated channels in cell-attached patches of cultured bovine aortic endothelial cells. Pflügers Arch. 431:1129–31
    [Google Scholar]
  72. 72.
    Romanenko VG, Fang Y, Byfield F, Travis AJ, Vandenberg CA et al. 2004. Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels. Biophys. J. 87:63850–61
    [Google Scholar]
  73. 73.
    Kusche-Vihrog K, Callies C, Fels J, Oberleithner H. 2010. The epithelial sodium channel (ENaC): Mediator of the aldosterone response in the vascular endothelium?. Steroids 75:8–9544–49
    [Google Scholar]
  74. 74.
    Wang S, Meng F, Mohan S, Champaneri B, Gu Y. 2009. Functional ENaC channels expressed in endothelial cells: a new candidate for mediating shear force. Microcirculation 16:3276–87
    [Google Scholar]
  75. 75.
    Sternak M, Bar A, Adamski MG, Mohaissen T, Marczyk B et al. 2018. The deletion of endothelial sodium channel a (αENaC) impairs endothelium-dependent vasodilation and endothelial barrier integrity in endotoxemia in vivo. Front. Pharmacol. 9:178
    [Google Scholar]
  76. 76.
    Knoepp F, Ashley Z, Barth D, Baldin JP, Jennings M et al. 2020. Shear force sensing of epithelial Na+ channel (ENaC) relies on N-glycosylated asparagines in the palm and knuckle domains of αENaC. PNAS 117:1717–26
    [Google Scholar]
  77. 77.
    Tarjus A, Maase M, Jeggle P, Martinez-Martinez E, Fassot C et al. 2017. The endothelial αENaC contributes to vascular endothelial function in vivo. PLOS ONE 12:9e0185319
    [Google Scholar]
  78. 78.
    Cosgun ZC, Sternak M, Fels B, Bar A, Kwiatkowski G et al. 2022. Rapid shear stress-dependent ENaC membrane insertion is mediated by the endothelial glycocalyx and the mineralocorticoid receptor. Cell. Mol. Life Sci. 79:235
    [Google Scholar]
  79. 79.
    Jeggle P, Callies C, Tarjus A, Fassot C, Fels J et al. 2013. Epithelial sodium channel stiffens the vascular endothelium in vitro and in Liddle mice. Hypertension 61:51053–59
    [Google Scholar]
  80. 80.
    Zhang J, Yuan HK, Chen S, Zhang ZR. 2022. Detrimental or beneficial: role of endothelial ENaC in vascular function. J. Cell Physiol. 237:129–48
    [Google Scholar]
  81. 81.
    Pérez FR, Venegas F, González M, Andrés S, Vallejos C et al. 2009. Endothelial epithelial sodium channel inhibition activates endothelial nitric oxide synthase via phosphoinositide 3-kinase/Akt in small-diameter mesenteric arteries. Hypertension 53:61000–7
    [Google Scholar]
  82. 82.
    Guo D, Liang S, Wang S, Tang C, Yao B et al. 2016. Role of epithelial Na+ channels in endothelial function. J. Cell Sci. 129:2290–97
    [Google Scholar]
  83. 83.
    Ashley Z, Mugloo S, McDonald FJ, Fronius M. 2018. Epithelial Na+ channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice. Am. J. Physiol. Heart Circ. Physiol. 314:5H1022–32
    [Google Scholar]
  84. 84.
    Gurney A, Manoury B. 2008. Two-pore potassium channels in the cardiovascular system. Eur. Biophys. J. 38:3305–18
    [Google Scholar]
  85. 85.
    Brohawn SG, Su Z, MacKinnon R. 2014. Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels. PNAS 111:93614–19
    [Google Scholar]
  86. 86.
    Lesage F, Terrenoire C, Romey G, Lazdunski M. 2000. Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J. Biol. Chem. 275:3728398–405
    [Google Scholar]
  87. 87.
    Patel AJ, Honoré E, Maingret F, Lesage F, Fink M et al. 1998. A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J. 17:154283–90
    [Google Scholar]
  88. 88.
    Brohawn SG. 2015. How ion channels sense mechanical force: insights from mechanosensitive K2P channels TRAAK, TREK1, and TREK2. Ann. N. Y. Acad. Sci. 1352:120–32
    [Google Scholar]
  89. 89.
    Honoré E, Patel AJ, Chemin J, Suchyna T, Sachs F. 2006. Desensitization of mechano-gated K2P channels. PNAS 103:186859
    [Google Scholar]
  90. 90.
    Schmidpeter PAM, Petroff JT 2nd, Khajoueinejad L, Wague A, Frankfater C et al. 2023. Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1. Nat. Commun. 14:1077
    [Google Scholar]
  91. 91.
    Garry A, Fromy B, Blondeau N, Henrion D, Brau F et al. 2007. Altered acetylcholine, bradykinin and cutaneous pressure-induced vasodilation in mice lacking the TREK1 potassium channel: the endothelial link. EMBO Rep. 8:4354–59
    [Google Scholar]
  92. 92.
    Rao AM, Hatcher JF, Kindy MS, Dempsey RJ. 1999. Arachidonic acid and leukotriene C4: role in transient cerebral ischemia of gerbils. Neurochem. Res. 24:101225–32
    [Google Scholar]
  93. 93.
    Maingret F, Patel AJ, Lesage F, Lazdunski M, Honoré E. 1999. Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J. Biol. Chem. 274:3826691–96
    [Google Scholar]
  94. 94.
    Chemin J, Patel AJ, Duprat F, Lauritzen I, Lazdunski M, Honoré E. 2005. A phospholipid sensor controls mechanogating of the K+ channel TREK-1. EMBO J. 24:144–53
    [Google Scholar]
  95. 95.
    Mathie A. 2007. Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors. J. Physiol. 578:2377–85
    [Google Scholar]
  96. 96.
    Takada Y, Kato C, Kondo S, Korenaga R, Ando J. 1997. Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress. Biochem. Biophys. Res. Commun. 240:3737–41
    [Google Scholar]
  97. 97.
    Chachisvilis M, Zhang YL, Frangos JA. 2006. G protein-coupled receptors sense fluid shear stress in endothelial cells. PNAS 103:4215463–68
    [Google Scholar]
  98. 98.
    Gudi S, Nolan JP, Frangos JA. 1998. Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. PNAS 95:52515–19
    [Google Scholar]
  99. 99.
    Yamamoto K, Ando J. 2015. Vascular endothelial cell membranes differentiate between stretch and shear stress through transitions in their lipid phases. Am. J. Physiol. Heart Circ. Physiol. 309:7H1178–85
    [Google Scholar]
  100. 100.
    Yamamoto K, Ando J. 2013. Endothelial cell and model membranes respond to shear stress by rapidly decreasing the order of their lipid phases. J. Cell Sci. 126:51227–34
    [Google Scholar]
  101. 101.
    Erdogmus S, Storch U, Danner L, Becker J, Winter M et al. 2019. Helix 8 is the essential structural motif of mechanosensitive GPCRs. Nat. Commun. 10:5784
    [Google Scholar]
  102. 102.
    Ozkan AD, Gettas T, Sogata A, Phaychanpheng W, Zhou M, Lacroix JJ. 2021. Mechanical and chemical activation of GPR68 probed with a genetically encoded fluorescent reporter. J. Cell Sci. 134:16jcs255455
    [Google Scholar]
  103. 103.
    dela Paz NG, Melchior B, Frangos JA. 2017. Shear stress induces Gαq/11 activation independently of G protein-coupled receptor activation in endothelial cells. Am. J. Physiol. Cell Physiol. 312:4C428–37
    [Google Scholar]
  104. 104.
    Liao JK, Homcy CJ. 1993. The G proteins of the Gαi and Gαq family couple the bradykinin receptor to the release of endothelium-derived relaxing factor. J. Clin. Investig. 92:52168–72
    [Google Scholar]
  105. 105.
    Hu Y, Chen M, Wang M, Li X. 2022. Flow-mediated vasodilation through mechanosensitive G protein-coupled receptors in endothelial cells. Trends Cardiovasc. Med. 32:261–70
    [Google Scholar]
  106. 106.
    Jung B, Obinata H, Galvani S, Mendelson K, Ding B-S et al. 2012. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev. Cell 23:3600–10
    [Google Scholar]
  107. 107.
    Cantalupo A, Gargiulo A, Dautaj E, Liu C, Zhang Y et al. 2017. S1PR1 (sphingosine-1-phosphate receptor 1) signaling regulates blood flow and pressure. Hypertension 70:2426–34
    [Google Scholar]
  108. 108.
    Vanlandewijck M, He L, Mäe MA, Andrae J, Ando K et al. 2018. A molecular atlas of cell types and zonation in the brain vasculature. Nature 554:7693475–80
    [Google Scholar]
  109. 109.
    Marullo S, Doly S, Saha K, Enslen H, Scott MGH, Coureuil M. 2020. Mechanical GPCR activation by traction forces exerted on receptor N-glycans. ACS Pharmacol. Transl. Sci. 3:2171–78
    [Google Scholar]
  110. 110.
    Harraz OF, Hill-Eubanks D, Nelson MT. 2020. PIP2: a critical regulator of vascular ion channels hiding in plain sight. PNAS 117:3420378–89
    [Google Scholar]
  111. 111.
    Reitsma S, Slaaf DW, Vink H, van Zandvoort MAMJ, oude Egbrink MGA. 2007. The endothelial glycocalyx: composition, functions, and visualization. Pflügers Arch. 454:3345–59
    [Google Scholar]
  112. 112.
    Tarbell JM, Simon SI, Curry F-RE. 2014. Mechanosensing at the vascular interface. Annu. Rev. Biomed. Eng. 16:505–32
    [Google Scholar]
  113. 113.
    Zeng Y, Zhang XF, Fu BM, Tarbell JM. 2018. The role of endothelial surface glycocalyx in mechanosensing and transduction. Mol. Cell. Tissue Eng. Vasc. Syst. 1097:1–27
    [Google Scholar]
  114. 114.
    Weinbaum S, Tarbell JM, Damiano ER. 2007. The structure and function of the endothelial glycocalyx layer. Annu. Rev. Biomed. Eng. 9:121–67
    [Google Scholar]
  115. 115.
    Nikmanesh M, Shi Z-D, Tarbell JM. 2012. Heparan sulfate proteoglycan mediates shear stress-induced endothelial gene expression in mouse embryonic stem cell-derived endothelial cells. Biotechnol. Bioeng. 109:2583–94
    [Google Scholar]
  116. 116.
    Harding IC, Mitra R, Mensah SA, Herman IM, Ebong EE. 2018. Pro-atherosclerotic disturbed flow disrupts caveolin-1 expression, localization, and function via glycocalyx degradation. J. Transl. Med. 16:1364
    [Google Scholar]
  117. 117.
    Ebong EE, Lopez-Quintero SV, Rizzo V, Spray DC, Tarbell JM. 2014. Shear-induced endothelial NOS activation and remodeling via heparan sulfate, glypican-1, and syndecan-1. Integr. Biol. 6:3338–47
    [Google Scholar]
  118. 118.
    Florian JA, Kosky JR, Ainslie K, Pang Z, Dull RO, Tarbell JM 2003. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ. Res. 93:10e136–42
    [Google Scholar]
  119. 119.
    Yen W, Cai B, Yang J, Zhang L, Zeng M et al. 2015. Endothelial surface glycocalyx can regulate flow-induced nitric oxide production in microvessels in vivo. PLOS ONE 10:1e0117133
    [Google Scholar]
  120. 120.
    Mochizuki S, Vink H, Hiramatsu O, Kajita T, Shigeto F et al. 2003. Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release. Am. J. Physiol. Heart Circ. Physiol. 285:2H722–26
    [Google Scholar]
  121. 121.
    Hecker M, Mulsch A, Bassenge E, Busse R. 1993. Vasoconstriction and increased flow: two principal mechanisms of shear stress-dependent endothelial autacoid release. Am. J. Physiol. Heart Circ. Physiol. 265:3H828–33
    [Google Scholar]
  122. 122.
    Kumagai R, Lu X, Kassab GS. 2009. Role of glycocalyx in flow-induced production of nitric oxide and reactive oxygen species. Free Radic. Biol. Med. 47:5600–7
    [Google Scholar]
  123. 123.
    Pahakis MY, Kosky JR, Dull RO, Tarbell JM. 2007. The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress. Biochem. Biophys. Res. Commun. 355:1228–33
    [Google Scholar]
  124. 124.
    Ruane-O'Hora T, Ahmeda A, Markos F. 2020. The vascular glycocalyx is not a mechanosensor in conduit arteries in the anesthetized pig. PeerJ 8:e8725
    [Google Scholar]
  125. 125.
    Cancel LM, Ebong EE, Mensah S, Hirschberg C, Tarbell JM. 2016. Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model. Atherosclerosis 252:136–46
    [Google Scholar]
  126. 126.
    Thi MM, Tarbell JM, Weinbaum S, Spray DC. 2004. The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: a “bumper-car” model. PNAS 101:4716483–88
    [Google Scholar]
  127. 127.
    Moon JJ, Matsumoto M, Patel S, Lee L, Guan J-L, Li S. 2005. Role of cell surface heparan sulfate proteoglycans in endothelial cell migration and mechanotransduction. J. Cell Physiol. 203:1166–76
    [Google Scholar]
  128. 128.
    Liu Y, Collins C, Kiosses WB, Murray AM, Joshi M et al. 2013. A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. J. Cell Biol. 201:6863–73
    [Google Scholar]
  129. 129.
    Fleming I, Fisslthaler B, Dixit M, Busse R. 2005. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. J. Cell Sci. 118:4103–11
    [Google Scholar]
  130. 130.
    Bagi Z, Frangos JA, Yeh JC, White CR, Kaley G, Koller A. 2005. PECAM-1 mediates NO-dependent dilation of arterioles to high temporal gradients of shear stress. Arterioscler. Thromb. Vasc. Biol. 25:81590–95
    [Google Scholar]
  131. 131.
    Masuda M, Osawa M, Shigematsu H, Harada N, Fujiwara K. 1997. Platelet endothelial cell adhesion molecule-1 is a major SH-PTP2 binding protein in vascular endothelial cells. FEBS Lett. 408:3331–36
    [Google Scholar]
  132. 132.
    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 437:7057426–31
    [Google Scholar]
  133. 133.
    Chiu YJ, McBeath E, Fujiwara K. 2008. Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation. J. Cell Biol. 182:4753–63
    [Google Scholar]
  134. 134.
    Osawa M, Masuda M, Kusano KI, Fujiwara K. 2002. Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: Is it a mechanoresponsive molecule?. J. Cell Biol. 158:4773–85
    [Google Scholar]
  135. 135.
    Tai LK, Zheng Q, Pan S, Jin ZG, Berk BC. 2005. Flow activates ERK1/2 and endothelial nitric oxide synthase via a pathway involving PECAM1, SHP2, and Tie2. J. Biol. Chem. 280:3329620–24
    [Google Scholar]
  136. 136.
    Govers R, Bevers L, De Bree P, Rabelink TJ. 2002. Endothelial nitric oxide synthase activity is linked to its presence at cell-cell contacts. Biochem. J. 361:Part 2193–201
    [Google Scholar]
  137. 137.
    Dusserre N, L'Heureux N, Bell KS, Stevens HY, Yeh J et al. 2004. PECAM-1 interacts with nitric oxide synthase in human endothelial cells: Implication for flow-induced nitric oxide synthase activation. Arterioscler. Thromb. Vasc. Biol. 24:101796–802
    [Google Scholar]
  138. 138.
    Liu Y, Bubolz AH, Shi Y, Newman PJ, Newman DK, Gutterman DD. 2006. Peroxynitrite reduces the endothelium-derived hyperpolarizing factor component of coronary flow-mediated dilation in PECAM-1-knockout mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290:157–65
    [Google Scholar]
  139. 139.
    Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, Schwartz MA. 2013. Fluid shear stress on endothelial cells modulates mechanical tension across VE-cadherin and PECAM-1. Curr. Biol. 23:111024–30
    [Google Scholar]
  140. 140.
    Sumpio BE, Yun S, Cordova AC, Haga M, Zhang J et al. 2005. MAPKs (ERK1/2, p38) and AKT can be phosphorylated by shear stress independently of platelet endothelial cell adhesion molecule-1 (CD31) in vascular endothelial cells. J. Biol. Chem. 280:1211185–91
    [Google Scholar]
  141. 141.
    Mehta V, Pang KL, Rozbesky D, Nather K, Keen A et al. 2020. The guidance receptor plexin D1 is a mechanosensor in endothelial cells. Nature 578:7794290–95
    [Google Scholar]
  142. 142.
    Uesugi K, Oinuma I, Katoh H, Negishi M. 2009. Different requirement for Rnd GTPases of R-Ras GAP activity of plexin-C1 and plexin-D1. J. Biol. Chem. 284:116743–51
    [Google Scholar]
  143. 143.
    Sandri C, Caccavari F, Valdembri D, Camillo C, Veltel S et al. 2012. The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling. Cell Res. 22:101479–501
    [Google Scholar]
  144. 144.
    Sinha B, Köster D, Ruez R, Gonnord P, Bastiani M et al. 2011. Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144:3402–13
    [Google Scholar]
  145. 145.
    Yu J, Bergaya S, Murata T, Alp IF, Bauer MP et al. 2006. Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J. Clin. Investig. 116:51284–91
    [Google Scholar]
  146. 146.
    Rizzo V, Sung A, Oh P, Schnitzer JE. 1998. Rapid mechanotransduction in situ at the luminal cell surface of vascular endothelium and its caveolae. J. Biol. Chem. 273:4126323–29
    [Google Scholar]
  147. 147.
    Rizzo V, McIntosh DP, Oh P, Schnitzer JE. 1998. In situ flow activates endothelial nitric oxide synthase in luminal caveolae of endothelium with rapid caveolin dissociation and calmodulin association. J. Biol. Chem. 273:5234724–29
    [Google Scholar]
  148. 148.
    Sonveaux P, Martinive P, DeWever J, Batova Z, Daneau G et al. 2004. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. Circ. Res. 95:2154–61
    [Google Scholar]
  149. 149.
    Radel C, Rizzo V. 2005. Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. Am. J. Physiol. Heart Circ. Physiol. 288:2936–45
    [Google Scholar]
  150. 150.
    Lolo FN, Pavón DM, Grande-García A, Elósegui-Artola A, Segatori VI et al. 2022. Caveolae couple mechanical stress to integrin recycling and activation. eLife 11:e82348
    [Google Scholar]
  151. 151.
    Frank PG, Woodman SE, Park DS, Lisanti MP. 2003. Caveolin, caveolae, and endothelial cell function. Arterioscler. Thromb. Vasc. Biol. 23:71161–68
    [Google Scholar]
  152. 152.
    Yamamoto K, Furuya K, Nakamura M, Kobatake E, Sokabe M, Ando J. 2011. Visualization of flow-induced ATP release and triggering of Ca2+ waves at caveolae in vascular endothelial cells. J. Cell Sci. 124:Part 203477–83
    [Google Scholar]
  153. 153.
    Wang N, Butler JP, Ingber DE. 1993. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:51111124–27
    [Google Scholar]
  154. 154.
    Matthews BD, Overby DR, Mannix R, Ingber DE. 2006. Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J. Cell Sci. 119:3508–18
    [Google Scholar]
  155. 155.
    Choquet D, Felsenfeld DP, Sheetz MP. 1997. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 88:139–48
    [Google Scholar]
  156. 156.
    Collins C, Guilluy C, Welch C, O'Brien ET, Hahn K et al. 2012. Localized tensional forces on PECAM-1 elicit a global mechanotransduction response via the integrin-RhoA pathway. Curr. Biol. 22:2087–94
    [Google Scholar]
  157. 157.
    Boyd NL, Park H, Yi H, Boo YC, Sorescu GP et al. 2003. Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 285:31113–22
    [Google Scholar]
  158. 158.
    Mackay CE, Leo MD, Fernández-Peña C, Hasan R, Yin W et al. 2020. Intravascular flow stimulates PKD2 (Polycystin-2) channels in endothelial cells to reduce blood pressure. eLife 9:e56655
    [Google Scholar]
  159. 159.
    Lisanti MP, Scherer PE, Vidugiriene J, Tang ZL, Hermanowski-Vosatka A et al. 1994. Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J. Cell Biol. 126:1111–26
    [Google Scholar]
  160. 160.
    Rizzo V, Morton C, DePaola N, Schnitzer JE, Davies PF. 2003. Recruitment of endothelial caveolae into mechanotransduction pathways by flow conditioning in vitro. Am. J. Physiol. Heart Circ. Physiol. 285:41720–29
    [Google Scholar]
  161. 161.
    Feron O, Dessy C, Moniotte S, Desager JP, Balligand JL. 1999. Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J. Clin. Investig. 103:6897–905
    [Google Scholar]
  162. 162.
    Friedrich EE, Hong Z, Xiong S, Zhong M, Di A et al. 2019. Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions. PNAS 116:2612980–85
    [Google Scholar]
  163. 163.
    Bartoli F, Debant M, Chuntharpursat-Bon E, Evans EL, Musialowski KE et al. 2022. Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity. J. Clin. Investig. 132:5e141775
    [Google Scholar]
  164. 164.
    Wang SP, Wang B, Shi Y, Möller T, Stegmeyer RI et al. 2022. Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis. Blood 140:3171–83
    [Google Scholar]
  165. 165.
    Retailleau K, Duprat F, Arhatte M, Ranade SS, Peyronnet R et al. 2015. Piezo1 in smooth muscle cells is involved in hypertension-dependent arterial remodeling. Cell Rep. 13:61161–71
    [Google Scholar]
  166. 166.
    Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR et al. 2014. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34:3611929–47
    [Google Scholar]
  167. 167.
    Saunders A, Macosko EZ, Wysoker A, Goldman M, Krienen FM et al. 2018. Molecular diversity and specializations among the cells of the adult mouse brain. Cell 174:41015–30.e16
    [Google Scholar]
  168. 168.
    Iadecola C. 2017. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 96:117–42
    [Google Scholar]
  169. 169.
    Cheng C, Tempel D, Van Haperen R, Van Der Baan A, Grosveld F et al. 2006. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 113:232744–53
    [Google Scholar]
  170. 170.
    Brooks AR, Lelkes PI, Rubanyi GM. 2004. Gene expression profiling of vascular endothelial cells exposed to fluid mechanical forces: relevance for focal susceptibility to atherosclerosis. Endothelium 11:145–57
    [Google Scholar]
  171. 171.
    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 Physiol. 273:2C572–78
    [Google Scholar]
  172. 172.
    Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI. 2006. Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J. Exp. Med. 203:92073–83
    [Google Scholar]
  173. 173.
    Orr AW, Sanders JM, Bevard M, Coleman E, Sarembock IJ, Schwartz MA. 2005. The subendothelial extracellular matrix modulates NF-κB activation by flow: a potential role in atherosclerosis. J. Cell Biol. 169:1191–202
    [Google Scholar]
  174. 174.
    Thoumine O, Nerem RM, Girard FR. 1995. Oscillatory shear stress and hydrostatic pressure modulate cell-matrix attachment proteins in cultured endothelial cells. In Vitro Cell. Dev. Biol. Anim. 31:45–54
    [Google Scholar]
  175. 175.
    Hsieh H-J, Cheng C-C, Wu S-T, Chiu J-J, Wung B-S, Wang DL. 1998. Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear-induced c-fos expression. J. Cell Physiol. 175:156–62
    [Google Scholar]
  176. 176.
    Mayet J, Hughes A. 2003. Cardiac and vascular pathophysiology in hypertension. Heart 89:91104–9
    [Google Scholar]
  177. 177.
    Harrison DG, Widder J, Grumbach I, Chen W, Weber M, Searles C. 2006. Endothelial mechanotransduction, nitric oxide and vascular inflammation. J. Intern. Med. 259:4351–63
    [Google Scholar]
  178. 178.
    Koide M, Harraz OF, Dabertrand F, Longden TA, Ferris HR et al. 2021. Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease. J. Clin. Investig. 131:18e149029
    [Google Scholar]
  179. 179.
    Ma S, Cahalan S, LaMonte G, Grubaugh ND, Zeng W et al. 2018. Common PIEZO1 allele in African populations causes RBC dehydration and attenuates Plasmodium infection. Cell 173:2443–55.e12
    [Google Scholar]
/content/journals/10.1146/annurev-physiol-042022-030946
Loading
/content/journals/10.1146/annurev-physiol-042022-030946
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error