Механочувствительные молекулярные взаимодействия в атерогенных районах артерий: развитие атеросклероза

Атеросклероз, грозное заболевание сердечно­сосудистой системы, развивается в местах изгибов и разветвлений артерий, где меняются направление и модуль вектора скорости тока крови, а следовательно, механическое воздействие на контактирующие с током крови эндотелиальные клетки. Обзор посвящен актуальным исследованиям развития атеросклероза: механобиохимическим событиям, преобразующим проатерогенный механический стимул тока крови – низкое и низкое/осциллирующее напряжение сдвига, оказываемое на стенки артерий, – в цепи биохимических реакций в эндотелиальных клетках, приводящих к экспрессии специфичных белков, вызывающих прогрессирование патологического процесса. Описаны стадии, системные факторы риска, а также важный гемодинамический фактор атерогенеза: низкое и низкое/осциллирующее напряжение сдвига, оказываемое током крови на эндотелиальные клетки, выстилающие стенки артерий. Показаны взаимодействия молекул клеточной адгезии, ответственные за развитие атеросклероза в условиях низкого и низкого/осциллирующего напряжения сдвига. Описаны активация регулятора экспрессии молекул клеточной адгезии – транскрипционного фактора NF­κB – и факторы, контролирующие его активацию в этих условиях. Описаны механочувствительные сигнальные пути, приводящие к экспрессии NF­κB в эндотелиальных клетках. Исследования механобиохимических сигнальных путей и взаимодействий, вовлеченных в прогрессирование атеросклероза, необходимы для разработки подходов, задерживающих или блокирующих развитие заболевания.

1. Alcaide P., Newton G., Auerbach S., Sehrawat S., Mayadas T.N., Golan D.E., Yacono P., Vincent P., Kowalczyk A., Luscinskas F.W. p120-Catenin regulates leukocyte transmigration through an effect on VE-cadherin phosphorylation. Blood. 2008;112(7):2770-2779. DOI 10.1182/blood-2008-03-147181.

2. Allingham M.J., van Buul J.D., Burridge K. ICAM-1-mediated, Srcand Pyk2-dependent vascular endothelial cadherin tyrosine phosphorylation is required for leukocyte transendothelial migration. J. Immunol. 2007;179(6):4053-4064. DOI 10.4049/jimmunol.179.6.4053.

3. Allport J.R., Muller W.A., Luscinskas F.W. Monocytes induce reversible focal changes in vascular endothelial cadherin complex during transendothelial migration under flow. J. Cell. Biol. 2000;148(1): 203-216. DOI 10.1083/jcb.148.1.203.

4. Amberger A., Maczek C., Jürgens G., Michaelis D., Schett G., Trieb K., Eberl T., Jindal S., Xu Q., Wick G. Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous endothelial cells in response to cytokines and oxidized low-density lipoproteins. Cell Stress Chaperones. 1997;2(2):94-103. DOI 10.1379/1466-1268(1997)002<0094:ceoive>2.3.co;2.

5. Arita-Okubo S., Kim-Kaneyama J.R., Lei X.F., Fu W.G., Ohnishi K., Takeya M., Miyauchi A., Honda H., Itabe H., Miyazaki T., Miyazaki A. Role of Hic-5 in the formation of microvilli-like structures and the monocyte-endothelial interaction that accelerates atherosclerosis. Cardiovasc. Res. 2015;105(3):361-371. DOI 10.1093/cvr/cvv003.

6. Barreiro O., Yanez-Mo M., Serrador J.M., Montoya M.C., VicenteManzanares M., Tejedor R., Furthmayr H., Sanchez-Madrid F. Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J. Cell Biol. 2002;157(7):1233-1245. DOI 10.1083/jcb.200112126.

7. Brand K., Page S., Rogler G., Bartsch A., Brandl R., Knuechel R., Page M., Kaltschmidt C., Baeuerle P.A., Neumeier D. Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J. Clin. Invest. 1996;97(7):1715-1722. DOI 10.1172/JCI118598.

8. Butcher M.J., Waseem T.C., Galkina E.V. Smooth muscle cell-derived interleukin-17C plays an atherogenic role via the recruitment of proinflammatory interleukin-17A + T cells to the aorta. Arterioscler. Thromb. Vasc. Biol. 2016;36(8):1496-1506. DOI 10.1161/ATVBAHA.116.307892.

9. Carlos T.M., Harlan J.M. Leukocyte-endothelial adhesion molecules. Blood. 1994;84(7):2068-2101. DOI 10.1111/j.1582-4934.2009.00811.x.

10. Carman C.V., Jun C.D., Salas A., Springer T.A. Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1. J. Immunol. 2003;171(11):6135-6144. DOI 10.4049/jimmunol.171.11.6135.

11. Carman C.V., Springer T.A. A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J. Cell Biol. 2004;167(2):377-388. DOI 10.1083/jcb.200404129.

12. Cecchi E., Giglioli C., Valente S., Lazzeri C., Gensini G.F., Abbate R., Mannini L. Role of hemodynamic shear stress in cardiovascular disease. Atherosclerosis. 2011;214(2):249-256. DOI 10.1016/j.atherosclerosis.2010.09.008.

13. Chang C.T., Shen M.Y., Lee A.S., Wang C.C., Chen W.Y., Chang C.M., Chang K.C., Stancel N., Chen C.H. Electronegative low-density lipoprotein increases the risk of ischemic lower-extremity peripheral artery disease in uremia patients on maintenance hemodialysis. Sci. Rep. 2017;7(1):4654-4662. DOI 10.1038/s41598-017-04063-3.

14. Charo I.F., Taubman M.B. Chemokines in the pathogenesis of vascular disease. Circ. Res. 2004;95(9):858-866. DOI 10.1161/01.RES.0000146672.10582.17.

15. Chen K.D., Li Y.S., Kim M., Li S., Yuan S., Chien S., Shyy J.Y. Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J. Biol. Chem. 1999;274(26):18393-18400. DOI 10.1074/jbc.274.26.18393.

16. Cheng C., Tempel D., van Haperen R., van der Baan A., Grosveld F., Daemen M.J., Krams R., de Crom R. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation. 2006;113(23):2744-2753. DOI 10.1161/CIRCULATIONAHA.105.590018.

17. Chiu Y.J., McBeath E., Fujiwara K. Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation. J. Cell Biol. 2008;182(4):753-763. DOI 10.1083/jcb.200801062.

18. Colic M., Pantovic S., Jeremic M., Jokovic V., Obradovic Z., Rosic M. Transport of low-density lipoprotein into the blood vessel wall during atherogenic diet in the isolated rabbit carotid artery. Circ. J. 2015;79(8):1846-1852. DOI 10.1253/circj.CJ-14-1316.

19. Collins C., Osborne L.D., Guilluy C., Chen Z., O’Brien E.T. 3rd, Reader J.S., Burridge K., Superfine R., Tzima E. Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells. Nat. Commun. 2014;5:3984. DOI 10.1038/ncomms4984.

20. Cuhlmann S., Van der Heiden K., Saliba D., Tremoleda J.L., Khalil M., Zakkar M., Chaudhury H., Luong le A., Mason J.C., Udalova I., Gsell W., Jones H., Haskard D.O., Krams R., Evans P.C. Disturbed blood flow induces RelA expression via c-Jun N-terminal kinase 1: a novel mode of NF-κB regulation that promotes arterial inflammation. Circ. Res. 2011;108(8):950-959. DOI 10.1161/CIRCRESAHA.110.233841.

21. Dai G., Kaazempur-Mofrad M.R., Natarajan S., Zhang Y., Vaughn S., Blackman B.R., Kamm R.D., García-Cardeña G., Gimbrone M.A. Jr. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc. Natl. Acad. Sci. USA. 2004;101(41):14871-14876. DOI 10.1073/pnas.0406073101.

22. Davis M.E., Grumbach I.M., Fukai T., Cutchins A., Harrison D.G. Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor kappaB binding. J. Biol. Chem. 2003; 279(1):163-168. DOI 10.1074/jbc.M307528200.

23. Davis R.J. Signal transduction by the JNK group of MAP kinases. Cell. 2000;103:239-252. DOI 10.1016/S0092-8674(00)00116-1.

24. Denis J.F., Scheckenbach K.E.L., Pfenniger A., Meens M.J., Krams R., Miquerol L., Taffet S., Chanson M., Delmar M., Kwak B.R. Connexin40 controls endothelial activation by dampening NFκB activation. Oncotarget. 2017;8(31):50972-50986. DOI 10.18632/oncotarget.16438.

25. Dumaz N., Marais R. Integrating signals between cAMP and the RAS/ RAF/MEK/ERK signalling pathways. FEBS J. 2005;272(14):3491-3504. DOI 10.1111/j.1742-4658.2005.04763.x.

26. Erbel C., Akhavanpoor M., Okuyucu D., Wangler S., Dietz A., Zhao L., Stellos K., Little K.M., Lasitschka F., Doesch A., Hakimi M., Dengler T.J., Giese T., Blessing E., Katus H.A., Gleissner C.A. IL-17A influences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis. J. Immunol. 2014;193(9):4344-4355. DOI 10.4049/jimmunol.1400181.

27. Feaver R.E., Gelfand B.D., Wang C., Schwartz M.A., Blackman B.R. Atheroprone hemodynamics regulate fibronectin deposition to create positive feedback that sustains endothelial inflammation. Circ. Res. 2010;106(11):1703-1711. DOI 10.1161/CIRCRESAHA.109.216283.

28. Frangos J.A., Eskin S.G., McIntire L.V., Ives C.L. Flow effects on prostacyclin production by cultured human endothelial cells. Science. 1985;227(4693):1477-1479. DOI 10.1126/science.3883488.

29. Garrett J.P., Lowery A.M., Adam A.P., Kowalczyk A.P., Vincent P.A. Regulation of endothelial barrier function by p120-catenin · VE-cadherin interaction. Mol. Biol. Cell. 2017;28(1):85-97. DOI 10.1091/mbc.E16-08-0616.

30. Gonzalez A.M., Cyrus B.F., Muller W.A. Targeted recycling of the lateral border recycling compartment precedes adherens junction dissociation during transendothelial migration. Am. J. Pathol. 2016; 186(5):1387-1402. DOI 10.1016/j.ajpath.2016.01.010.

31. Gudi S.R., Clark C.B., Frangos J.A. Fluid flow rapidly activates G proteins in human endothelial cells. Involvement of G proteins in mechanochemical signal transduction. Circ. Res. 1996;79(4):834-839. DOI 10.1161/01.RES.79.4.834.

32. Gudi S., Huvar I., White C.R., McKnight N.L., Dusserre N., Boss G.R., Frangos J.A. Rapid activation of Ras by fluid flow is mediated by Galpha(q) and Gbetagamma subunits of heterotrimeric G proteins in human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2003; 23(6):994-1000. DOI 10.1161/01.ATV.0000073314.51987.84.

33. Gudi S., Nolan J.P., Frangos J.A. Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. Proc. Natl. Acad. Sci. USA. 1998;95(5):2515-2519. DOI 10.1073/PNAS.95.5.2515.

34. Hajra L., Evans A.I., Chen M., Hyduk S.J., Collins T., Cybulsky M.I. The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc. Natl. Acad. Sci. USA. 2000;97(16):9052-9057. DOI 10.1073/pnas.97.16.9052.

35. Harrison M., Smith E., Ross E., Krams R., Segers D., Buckley C.D., Nash G.B., Rainger G.E. The role of platelet-endothelial cell adhesion molecule-1 in atheroma formation varies depending on the sitespecific hemodynamic environment. Arterioscler. Thromb. Vasc. Biol. 2013;33(4):694-701. DOI 10.1161/ATVBAHA.112.300379.

36. Hughes P.E., Pfaff M. Integrin affinity modulation. Trends. Cell Biol. 1998;8(9):359-364. DOI 10.1016/s0962-8924(98)01339-7.

37. Hung O.Y., Molony D., Corban M.T., Rasoul-Arzrumly E., Maynard C., Eshtehardi P., Dhawan S., Timmins L.H., Piccinelli M., Ahn S.G., Gogas B.D., McDaniel M.C., Quyyumi A.A., Giddens D.P., Samady H. Comprehensive assessment of coronary plaque progression with advanced intravascular imaging, physiological measures, and wall shear stress: a pilot double-blinded randomized controlled clinical trial of nebivolol versus atenolol in nonobstructive coronary artery disease. J. Am. Heart. Assoc. 2016;5(1):e002764. DOI 10.1161/JAHA.115.002764.

38. Huo Y., Ley K. Adhesion molecules and atherogenesis. Acta Physiol. Scand. 2001;173(1):35-43. DOI 10.1046/j.1365-201X.2001.00882.x.

39. Hynes R.O. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110(6):673-87. DOI 10.1016/s0092-8674(02)00971-6.

40. Jalali S., del Pozo M.A., Chen K., Miao H., Li Y., Schwartz M.A., Shyy J.Y., Chien S. Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc. Natl. Acad. Sci. USA. 2001;98(3):1042-1046. DOI 10.1073/pnas.98.3.1042.

41. Johnson D.S., Chen Y.H. Ras family of small GTPases in immunity and inflammation. Curr. Opin. Pharmacol. 2012;12(4):458-463. DOI 10.1016/j.coph.2012.02.003.

42. Ku D.N., Giddens D.P., Zarins C.K., Glagov S. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis. 1985;5(3):293-302. DOI 10.1161/01.ATV.5.3.293.

43. Kume N., Cybulsky M.I., Gimbrone M.A.Jr. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J. Clin. Invest. 1992;90(3):1138-1144. DOI 10.1172/JCI115932.

44. Ledebur H.C., Parks T.P. Transcriptional regulation of the intercellular adhesion molecule-1 gene by inflammatory cytokines in human endothelial cells. Essential roles of a variant NF-kappa B site and p65 homodimers. J. Biol. Chem. 1995;270(2):933-943. DOI 10.1074/jbc.270.2.933.

45. Libby P., Buring J.E., Badimon L., Hansson G.K., Deanfield J., Bittencourt M.S., Tokgözoğlu L., Lewis E.F. Atherosclerosis. Nat. Rev. Dis. Primers. 2019;5(1):56. DOI 10.1038/s41572-019-0106-z.

46. Liu Y., Sweet D.T., Irani-Tehrani M., Maeda N., Tzima E. Shc coordinates signals from intercellular junctions and integrins to regulate flow-induced inflammation. J. Cell Biol. 2008;182(1):185-196. DOI 10.1083/jcb.200709176.

47. Luscinskas F.W., Ding H., Tan P., Cumming D., Tedder T.F., Gerritsen M.E. L- and P-selectins, but not CD49d (VLA-4) integrins, mediate monocyte initial attachment to TNF-alpha-activated vascular endothelium under flow in vitro. J. Immunol. 1996;157(1):326-335.

48. Luscinskas F.W., Kansas G.S., Ding H., Pizcueta P., Schleiffenbaum B.E., Tedder T.F., Gimbrone M.A. Jr. Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, beta 1-integrins, and beta 2-integrins. J. Cell Biol. 1994;125(6):1417-1427. DOI 10.1083/jcb.125.6.1417.

49. Mamdouh Z., Chen X., Pierini L.M., Maxfield F.R., Muller W.A. Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis. Nature. 2003;421(6924):748-753. DOI 10.1038/nature01300.

50. Mamdouh Z., Kreitzer G.E., Muller W.A. Leukocyte transmigration requires kinesin-mediated microtubule-dependent membrane trafficking from the lateral border recycling compartment. J. Exp. Med. 2008;205(4):951-966. DOI 10.1084/jem.20072328.

51. Mamdouh Z., Mikhailov A., Muller W.A. Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment. J. Exp. Med. 2009;206(12):2795-2808. DOI 10.1084/jem.20082745.

52. Martin T., Cardarelli P.M., Parry G.C., Felts K.A., Cobb R.R. Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NFkappa B and AP-1. Eur. J. Immunol. 1997;27(5):1091-1097. DOI 10.1002/eji.1830270508.

53. McCormick F. Signal transduction. How receptors turn Ras on. Nature. 1993;363(6424):15-16. DOI 10.1038/363015a0.

54. Mohan S., Mohan N., Valente A.J., Sprague E.A. Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion. Am. J. Physiol. 1999;276(5):C1100-1107. DOI 10.1152/ajpcell.1999.276.5.C1100.

55. Morbiducci U., Kok A.M., Kwak B.R., Stone P.H., Steinman D.A., Wentzel J.J. Atherosclerosis at arterial bifurcations: evidence for the role of haemodynamics and geometry. Thromb. Haemost. 2016; 115(3):484-492. DOI 10.1160/TH15-07-0597.

56. Nagel T., Resnick N., Dewey C.F. Jr., Gimbrone M.A. Jr. Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arterioscler. Thromb. Vasc. Biol. 1999;19(8):1825-1834. DOI 10.1161/01.ATV.19.8.1825.

57. Nebuloni L., Kuhn G.A., Müller R. A comparative analysis of watersoluble and blood-pool contrast agents for in vivo vascular imaging with micro-CT. Acad. Radiol. 2013;20(10):1247-1255. DOI 10.1016/j.acra.2013.06.003.

58. Neish A.S., Williams A.J., Palmer H.J., Whitley M.Z., Collins T. Functional analysis of the human vascular cell adhesion molecule 1 promoter. J. Exp. Med. 1992;176(6):1583-1593. DOI 10.1084/jem.176.6.1583.

59. Oeckinghaus A., Hayden M.S., Ghosh S. Crosstalk in NF-κB signaling pathways. Nat. Immunol. 2011;12(8):695-708. DOI 10.1038/ni.2065.

60. O’Keeffe L.M., Muir G., Piterina A.V., McGloughlin T. Vascular cell adhesion molecule-1 expression in endothelial cells exposed to physiological coronary wall shear stresses. J. Biomech. Eng. 2009; 131(8):081003. DOI 10.1115/1.3148191.

61. Orr A.W., Sanders J.M., Bevard M., Coleman E., Sarembock I.J., Schwartz M.A. The subendothelial extracellular matrix modulates NF-kappaB activation by flow: a potential role in atherosclerosis. J. Cell Biol. 2005;169(1):191-202. DOI 10.1083/jcb.200410073.

62. Otsuka F., Kramer M.C., Woudstra P., Yahagi K., Ladich E., Finn A.V., de Winter R.J., Kolodgie F.D., Wight T.N., Davis H.R., Joner M., Virmani R. Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: a pathology study. Atherosclerosis. 2015;241(2):772-782. DOI 10.1016/j.atherosclerosis.2015.05.011.

63. Otte L.A., Bell K.S., Loufrani L., Yeh J.-C., Melchior B., Dao D.N., Stevens H.Y., White C.R., Frangos J.A. Rapid changes in shear stress induce dissociation of a G alpha(q/11)-platelet endothelial cell adhesion molecule-1 complex. J. Physiol. 2009;587(Pt.10):2365-2373. DOI 10.1113/jphysiol.2009.172643.

64. Ozerova I.N., Metelskaya V.A., Gavrilova N.E. Atherogenic normolipidemia in men with coronary atherosclerosis: some peculiarities of subfractional distribution of apo B-containing lipoproteins. Ateroscleroz = Atherosclerosis. 2018;14(3):5-11. DOI 10.15372/ATER20180301. (in Russian)

65. Paddock C., Zhou D., Lertkiatmongkol P., Newman P.J., Zhu J. Structural basis for PECAM-1 homophilic binding. Blood. 2016;127(8): 1052-1061. DOI 10.1182/blood-2015-07-660092.

66. Paz dela N.G., Melchior B., Shayo F.Y., Frangos J.A. Heparan sulfates mediate the interaction between platelet endothelial cell adhesion molecule-1 (PECAM-1) and the Gαq/11 subunits of heterotrimeric G proteins. J. Biol. Chem. 2014;289(11):7413-7424. DOI 10.1074/jbc.M113.542514.

67. Peters W., Charo I.F. Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis: lessons from knockout mice. Curr. Opin. Lipidol. 2001;12(2):175-180. DOI 10.1097/00041433-200104000-00011.

68. Resnick N., Collins T., Atkinson W., Bonthron D.T., Dewey C.F. Jr., Gimbrone M.A. Jr. Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc. Natl. Acad. Sci. USA. 1993;90(10):4591-4595. DOI 10.1073/pnas.90.10.4591.

69. Sahebkar A., Morris D.R., Biros E., Golledge J. Association of single nucleotide polymorphisms in the gene encoding platelet endothelial cell adhesion molecule-1 with the risk of myocardial infarction: a systematic review and meta-analysis. Thromb. Res. 2013;132(2):227-233. DOI 10.1016/j.thromres.2013.07.007.

70. Sakellarios A.I, Papafaklis M.I., Siogkas P., Athanasiou L.S., Exarchos T.P., Stefanou K., Bourantas C.V., Naka K.K., Michalis L.K., Parodi O., Fotiadis D.I. Patient-specific computational modeling of subendothelial LDL accumulation in a stenosed right coronary artery: effect of hemodynamic and biological factors. Am. J. Physiol. Heart Circ. Physiol. 2013;304(11):H1455-70. DOI 10.1152/ajpheart.00539.2012.

71. Schober A., Siess W. Lysophosphatidic acid in atherosclerotic diseases. Br. J. Pharmacol. 2012;167(3):465-482. DOI 10.1111/j.1476-5381.2012.02021.x.

72. Shaw S.K., Bamba P.S., Perkins B.N., Luscinskas F.W. Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium. J. Immunol. 2001;167(4):2323-2330. DOI 10.4049/jimmunol.167.4.2323.

73. Shimada H., Rajagopalan L.E. Rho kinase-2 activation in human endothelial cells drives lysophosphatidic acid-mediated expression of cell adhesion molecules via NF-kappaB p65. J. Biol. Chem. 2010; 285(17):12536-12542. DOI 10.1074/jbc.M109.099630.

74. Sigal A., Bleijs D.A., Grabovsky V., van Vliet S.J., Dwir O., Figdor C.G., van Kooyk Y., Alon R. The LFA-1 integrin supports rolling adhesions on ICAM-1 under physiological shear flow in a permissive cellular environment. J. Immunol. 2000;165(1):442. DOI 10.4049/jimmunol.165.1.442.

75. Simon M.I., Strathmann M.P., Gautam N. Diversity of G proteins in signal transduction. Science. 1991;252(5007):802-808. DOI 10.1126/science.1902986.

76. Snyder J.L., McBeath E., Thomas T.N., Chiu Y.J., Clark R.L., Fujiwara K. Mechanotransduction properties of the cytoplasmic tail of PECAM-1. Biol. Cell. 2017;109(8):312-321. DOI 10.1111/boc.201600079.

77. Soulis J.V., Farmakis T.M., Giannoglou G.D., Louridas G.E. Wall shear stress in normal left coronary artery tree. J. Biomech. 2006;39(4): 742-749. DOI 10.1016/j.jbiomech.2004.12.026.

78. Spiecker M., Peng H.B., Liao J.K. Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IkappaBalpha. J. Biol. Chem. 1997;272(49):30969-30974. DOI 10.1074/jbc.272.49.30969.

79. Suo J., Ferrara D.E., Sorescu D., Guldberg R.E., Taylor W.R., Giddens D.P. Hemodynamic shear stresses in mouse aortas – implications for atherogenesis. Arterioscler. Thromb. Vasc. Biol. 2007;27: 346-351. DOI 10.1161/01.ATV.0000253492.45717.46.

80. Timmins L.H., Molony D.S., Eshtehardi P., McDaniel M.C., Oshinski J.N., Giddens D.P., Samady H. Oscillatory wall shear stress is a dominant flow characteristic affecting lesion progression patterns and plaque vulnerability in patients with coronary artery disease. J. R. Soc. Interface. 2017;14(127):20160972. DOI 10.1098/rsif.2016.0972.

81. Timmins L.H., Molony D.S., Eshtehardi P., McDaniel M.C., Oshinski J.N., Samady H., Giddens D.P. Focal association between wall shear stress and clinical coronary artery disease progression. Ann. Biomed. Eng. 2015;43(1):94-106. DOI 10.1007/s10439-014-1155-9.

82. Tzima E., del Pozo M.A., Shattil S.J., Chien S., Schwartz M.A. Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. EMBO J. 2001;20(17): 4639-4647. DOI 10.1093/emboj/20.17.4639.

83. Tzima E., Irani-Tehrani M., Kiosses W.B., Dejana E., Schultz D.A., Engelhardt B., Cao G., DeLisser H., Schwartz M.A. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature. 2005;437(7057):426-431. DOI 10.1038/nature03952.

84. Virani S.S., Alonso A., Benjamin E.J., Bittencourt M.S., Callaway C.W., Carson A.P., Chamberlain A.M., Chang A.R., Cheng S., Delling F.N., ..., Stokes A., Tirschwell D.L., VanWagner L.B., Tsao C.W., American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-e596. DOI 10.1161/CIR.0000000000000757.

85. Whitley M.Z., Thanos D., Read M.A., Maniatis T., Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol. Cell Biol. 1994;14(10):6464-6475. DOI 10.1128/mcb.14.10.6464.

86. Wu C., Huang R.T., Kuo C.H., Kumar S., Kim C.W., Lin Y.C., Chen Y.J., Birukova A., Birukov K.G., Dulin N.O., Civelek M., Lusis A.J., Loyer X., Tedgui A., Dai G., Jo H., Fang Y. Mechanosensitive PPAP2B regulates endothelial responses to atherorelevant hemodynamic forces. Circ. Res. 2015;117(4):e41-e53. DOI 10.1161/CIRCRESAHA.117.306457.

87. Xia T., Liu X., Du C.J., Jin X., Kong X.Q., Li G. Association of Leu125Val polymorphisms in the PECAM-1 gene with the risk of coronary heart disease: a meta-analysis. Int. J. Clin. Exp. Med. 2015; 8(2):2219-2225.

88. Xing R., De Wilde D., McCann G., Ridwan Y., Schrauwen J.T., van der Steen A.F., Gijsen F.J., Van der Heiden K. Contrast-enhanced microCT imaging in murine carotid arteries: a new protocol for computing wall shear stress. Biomed. Eng. Online. 2016;15(Suppl.2):156. DOI 10.1186/s12938-016-0270-2.

89. Yamamoto K., Ando J. Emerging role of plasma membranes in vascular endothelial mechanosensing. Circ. J. 2018;82(11):2691-2698. DOI 10.1253/circj.CJ-18-0052.

90. Yeh J.-C., Otte L.A., Frangos J.A. Regulation of G protein-coupled receptor activities by the platelet-endothelial cell adhesion molecule, PECAM-1. Biochemistry. 2008;47(34):9029-9039. DOI 10.1021/bi8003846.

91. Yu X.H., Zheng X.L., Tang C.K. Nuclear factor-κB activation as a pathological mechanism of lipid metabolism and atherosclerosis. Adv. Clin. Chem. 2015;70:1-30. DOI 10.1016/bs.acc.2015.03.004.

92. Yung Y.C., Stoddard N.C., Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J. Lipid Res. 2014;55(7): 1192-1214. DOI 10.1194/jlr.R046458.

93. Yurdagul A.Jr., Chen J., Funk S.D., Albert P., Kevil C.G., Orr A.W. Altered nitric oxide production mediates matrix-specific PAK2 and NF-κB activation by flow. Mol. Biol. Cell. 2013;24(3):398-408. DOI 10.1091/mbc.E12-07-0513.

94. Yurdagul A.Jr., Sulzmaier F.J, Chen X.L., Pattillo C.B., Schlaepfer D.D., Orr A.W. Oxidized LDL induces FAK-dependent RSK signaling to drive NF-κB activation and VCAM-1 expression. J. Cell Sci. 2016;129(8):1580-1591. DOI 10.1242/jcs.182097.

95. Zakkar M., Chaudhury H., Sandvik G., Enesa K., Luong le A., Cuhlmann S., Mason J.C., Krams R., Clark A.R., Haskard D.O., Evans P.C. Increased endothelial mitogen-activated protein kinase phosphatase-1 expression suppresses proinflammatory activation at sites that are resistant to atherosclerosis. Circ. Res. 2008;103(7): 726-732. DOI 10.1161/CIRCRESAHA.108.183913.

96. Zhang W., Tang T., Nie D., Wen S., Jia C., Zhu Z., Xia N., Nie S., Zhou S., Jiao J., Dong W., Lu B., Xu T., Sun B., Lu Y., Li Y., Cheng L., Liao Y., Cheng X. IL-9 aggravates the development of atherosclerosis in ApoE-/- mice. Cardiovasc. Res. 2015;106(3):453-464. DOI 10.1093/cvr/cvv110.

97. Zou Y., Huang X., Feng L., Hou J., Xing L., Yu B. Localization of in-stent neoatherosclerosis in relation to curvatures and bifurcations after stenting. J. Thorac. Dis. 2016;8(12):3530-3536. DOI 10.21037/jtd.2016.11.108.