The role of endothelium in atherogenesis: dependence of atherosclerosis development on the properties of vessel endothelium

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Abstract

This review discusses development of atherosclerosis as based on the evidence for its dependence on the properties of vessel endothelium. There is a detailed description of the mechanisms of atherogenesis, that were studied earlier, of the processes of endothelial transport, including caveola-dependent pathway and also the hemodynamic hypothesis of atherosclerosis development. The possibilities of the direct and receptor-mediated lipoprotein transcytosis through the endothelial barrier were discussed. A special attention was paid to the physiological function of autophagy responsible for the intracellular lipoprotein transport.

About the authors

Nina S. Parfenova

FSBSI Institute of Experimental Medicine

Author for correspondence.
Email: nina.parf@mail.ru
SPIN-code: 9415-0241
Scopus Author ID: 7003709364
ResearcherId: E-66722014

PhD, Senior Researcher, Laboratory of Lipoproteins, Department of Biochemistry

Russian Federation, Saint Petersburg

References

  1. Аймагамбетова А.О. Атерогенез и воспаление. Обзор литературы // Наука и здравоохранение. – 2016. – № 1. – С. 24–39. [Aimagambetova AO. Аtherogenesis and inflammation. Nauka I zdravookhranenie. 2016;(1):24-39. (In Russ.)]
  2. Anichkov N, Chalatov S. Über experimentelle Cholesterinsteatose: Ihre Bedeutung für die Entstehung einiger pathologischer Prozessen. Zentrbl Allg Pathol Pathol Anat. 1913:24:21-29.
  3. Лиходед В.Г., Бондаренко В.М., Гинцбург А.Л. Экзогенные и эндогенные факторы в патогенезе атеросклероза. Рецепторная теория атерогенеза // Российский кардиологический журнал. – 2010. – Т. 15. – № 2. – С. 92–96. [Likhoded VG, Bondarenko VM, Gintzburg AL. Exogenous and endogenous factors in atherosclerosis pathogenesis. Receptor theory of atherogenesis. Russian journal of cardiology. 2010;15(2):92-96. (In Russ.)]
  4. Adler I. Studies in experimental atherosclerosis: a preliminary report. J Exp Med. 1914;20(2):93-107. https://doi.org/10.1084/jem.20.2.93.
  5. Ross R, Glomset JA. Atherosclerosis and the arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science. 1973;180(4093):1332-1339. https://doi.org/10.1126/science.180.4093.1332.
  6. Лазебник Л.Б. К 125-летию со дня рождения Н.Н. Аничкова // Клиническая геронтология. – 2011. – Т. 17. – № 1–2. – С. 81–83. [Lazebnik LB. The 125-jubilee of N.N. Anichkov’s birth. Klinicheskaia gerontologiia. 2011;17(1-2):81-83. (In Russ.)]
  7. Oncley JL. Lipoproteins of human plasma. Harvey Lect. 1954-1955;50:71-91.
  8. Gofman JW, Jones HB, Lindgren FT, et al. Blood lipids and human atherosclerosis. Circulation. 1950;2(2):161-178. https://doi.org/10.1161/01.cir.2.2.161.
  9. Durrington P. Dyslipidaemia. Lancet. 2003;362(9385): 717-731. https://doi.org/10.1016/s0140-6736(03)14234-1.
  10. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232(4746):34-47. https://doi.org/10.1126/science.3513311.
  11. Dominiczak MH, Caslake MJ. Apolipoproteins: metabolic role and clinical biochemistry applications. Ann Clin Biochem. 2011;48(Pt 6):498-515. https://doi.org/10.1258/acb.2011.011111.
  12. Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007;116(16):1832-1844. https://doi.org/10.1161/CIRCULATIONAHA.106.676890.
  13. Cohn JS, Marcoux C, Davignon J. Detection, quantification, and characterization of potentially atherogenic triglyceride-rich remnant lipoproteins. Arterioscler Thromb Vasc Biol. 1999;19(10):2474-2486. https://doi.org/10.1161/01.atv.19.10.2474.
  14. Mann CJ, Yen FT, Grant AM, Bihain BE. Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia. J Clin Invest. 1991;88(6):2059-2066. https://doi.org/10.1172/JCI115535.
  15. Havel RJ. The formation of LDL: mechanisms and regulation. J Lipid Res. 1984;25(13):1570-1576.
  16. Florentin M, Liberopoulos EN, Wierzbicki AS, Mikhailidis DP. Multiple actions of high-density lipoprotein. Curr Opin Cardiol. 2008;23(4):370-378. https://doi.org/10.1097/HCO.0b013e3283043806.
  17. Bruckert E, Hansel B. HDL-c is a powerful lipid predictor of cardiovascular diseases. Int J Clin Pract. 2007;61(11):1905-1913. https://doi.org/10.1111/j.1742-1241.2007.01509.x.
  18. Parton RG, Tillu VA, Collins BM. Caveolae. Curr Biol. 2018;28(8):R402-R405. https://doi.org/10.1016/j.cub.2017. 11.075.
  19. Lamaze C, Tardif N, Dewulf M, et al. The caveolae dress code: structure and signaling. Curr Opin Cell Biol. 2017;47:117-125. https://doi.org/10.1016/j.ceb.2017. 02.014.
  20. Lisanti MP, Tang Z, Scherer PE, et al. Caveolae, transmembrane signalling and cellular transformation. Mol Membr Biol. 1995;12(1):121-124. https://doi.org/10.3109/ 09687689509038506.
  21. Kurzchalia TV, Partan RG. Membrane microdomains and caveolae. Curr Opin Cell Biol. 1999;11(4):424-431. https://doi.org/10.1016/s0955-0674(99)80061-1.
  22. Williams TM, Lisanti MP. Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am J Physiol Cell Physiol. 2005;288(3):C494-506. https://doi.org/10.1152/ajpcell.00458.2004.
  23. Pelkmans L, Kartenbeck J, Helenius A. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol. 2001;3(5):473-483. https://doi.org/10.1038/35074539.
  24. Shin JS, Gao Z, Abraham SN. Involvement of cellular caveolae in bacterial entry into mast cells. Science. 2000;289(5480):785-788. https://doi.org/10.1126/science. 289.5480.785.
  25. Hayashi K, Matsuda S, Machida K, et al. Invasion activating caveolin-1 mutation in human scirrhous breast cancers. Cancer Res. 2001;61(6):2361-2364.
  26. Williams TM, Cheung MW, Park DS, et al. Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice. Mol Biol Cell. 2003;14(3):1027-1042. https://doi.org/10.1091/mbc.e02-08-0503.
  27. Woodman SE, Sotgia F, Galbiati F, et al. Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases. Neurology. 2004;62(4):538-543. https://doi.org/10.1212/wnl.62.4.538.
  28. Parton RG, Simons K. The multiple faces of caveolae. Nat Rev Mol Cell Biol. 2007;8(3):185-194. https://doi.org/10.1038/nrm2122.
  29. Fra AM, Williamson E, Simons K, Parton RG. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc Natl Acad Sci U S A. 1995;92(19):8655-8659. https://doi.org/10.1073/pnas.92.19.8655.
  30. Drab M, Verkade P, Elger M, et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science. 2001;293(5539):2449-2452. https://doi.org/10.1126/science.1062688.
  31. Galbiati F, Engelman JA, Volonte D, et al. Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and t-tubule abnormalities. J Biol Chem. 2001;276(24):21425-21433. https://doi.org/10.1074/jbc.M100828200.
  32. Zhang X, Sessa WC, Fernandez-Hernando C. Endothelial transcytosis of lipoproteins in atherosclerosis. Front Cardiovasc Med. 2018;5:130. https://doi.org/10.3389/fcvm.2018.00130.
  33. Rahimi N. Defenders and challengers of endothelial barrier function. Front Immunol. 2017;8:1847. https://doi.org/10.3389/fimmu.2017.01847.
  34. J MS, Graindorge A, Soldati-Favre D. New insights into parasite rhomboid proteases. Mol Biochem Parasitol. 2012;182(1-2):27-36. https://doi.org/10.1016/j.molbiopara.2011.11.010.
  35. Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev. 2006;86(1):279-367. https://doi.org/10.1152/physrev.00012.2005.
  36. Minshall RD, Malik AB. Transport across the endothelium: regulation of endothelial permeability. Handb Exp Pharmacol. 2006(176 Pt 1):107-144. https://doi.org/10.1007/ 3-540-32967-6_4.
  37. Fung KYY, Fairn GD, Lee WL. Transcellular vesicular transport in epithelial and endothelial cells: Challenges and opportunities. Traffic. 2018;19(1):5-18. https://doi.org/10.1111/tra.12533.
  38. Thuenauer R, Muller SK, Romer W. Pathways of protein and lipid receptor-mediated transcytosis in drug delivery. Expert Opin Drug Deliv. 2017;14(3):341-351. https://doi.org/ 10.1080/17425247.2016.1220364.
  39. Ramirez CM, Zhang X, Bandyopadhyay C, et al. Caveolin-1 regulates atherogenesis by attenuating low-density lipoprotein transcytosis and vascular inflammation independently of endothelial nitric oxide synthase activation. Circulation. 2019;140(3):225-239. https://doi.org/10.1161/CIRCULATIONAHA.118.038571.
  40. Glass CK, Witztum JL. Atherosclerosis. Cell. 2001;104(4):503-516. https://doi.org/10.1016/s0092-8674 (01)00238-0.
  41. Wang Z, Tiruppathi C, Cho J, et al. Delivery of nanoparticle: complexed drugs across the vascular endothelial barrier via caveolae. IUBMB Life. 2011;63(8):659-667. https://doi.org/10.1002/iub.485.
  42. Thoma R. Über die Abhängigkeit der Bindegewebsneubildung in der Arterienintima von den mechanischen Bedingungen des Blutumlaufes. Virchows Arch. 1883;93:443-505. https://doi.org/10.1007/BF02324120.
  43. Wolkoff K. Über die histologische Struktur der Coronararterien des menschlichen Herzens. Virchows Arch. 1923;241:42-58. https://doi.org/10.1007/BF01942462.
  44. Wolkoff K. Über die Altersveränderungen der Arterien bei Tieren. Virchows Arch. 1924;252:208-228. https://doi.org/10.1007/BF01960728.
  45. Stary HC. Composition and classification of human atherosclerotic lesions. Virchows Arch A Pathol Anat Histopathol. 1992;421(4):277-290. https://doi.org/10.1007/bf01660974.
  46. Zarins CK, Giddens DP, Bharadvaj BK, et al. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res. 1983;53(4):502-514. https://doi.org/10.1161/01.res.53.4.502.
  47. Albuquerque ML, Waters CM, Savla U, et al. Shear stress enhances human endothelial cell wound closure in vitro. Am J Physiol Heart Circ Physiol. 2000;279(1):H293-302. https://doi.org/10.1152/ajpheart.2000.279.1.H293.
  48. Dewey CF, Jr., Bussolari SR, Gimbrone MA, Jr., Davies PF. The dynamic response of vascular endothelial cells to fluid shear stress. J Biomech Eng. 1981;103(3):177-185. https://doi.org/10.1115/1.3138276.
  49. Diamond SL, Sharefkin JB, Dieffenbach C, et al. Tissue plasminogen activator messenger RNA levels increase in cultured human endothelial cells exposed to laminar shear stress. J Cell Physiol. 1990;143(2):364-371. https://doi.org/10.1002/jcp.1041430222.
  50. Dimmeler S, Haendeler J, Rippmann V, et al. Shear stress inhibits apoptosis of human endothelial cells. FEBS Letters. 1996;399(1-2):71-74. https://doi.org/10.1016/s0014-5793(96)01289-6.
  51. Frangos JA, Eskin SG, McIntire LV, Ives CL. Flow effects on prostacyclin production by cultured human endothelial cells. Science. 1985;227(4693):1477-1479. https://doi.org/10.1126/science.3883488.
  52. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83(5):1774-1777. https://doi.org/10.1172/JCI114081.
  53. Grabowski EF, Jaffe EA, Weksler BB. Prostacyclin production by cultured endothelial cell monolayers exposed to step increases inshear stress. J Lab Clin Med. 1985;105(1):36-43. https://doi.org/10.5555/uri:pii:0022214385900861.
  54. Grabowski EF, Reininger AJ, Petteruti PG, et al. Shear stress decreases endothelial cell tissue factor activity by augmenting secretion of tissue factor pathway inhibitor. Arterioscler Thromb Vasc Biol. 2001;21(1):157-162. https://doi.org/10.1161/01.atv.21.1.157.
  55. Helmlinger G, Geiger RV, Schreck S, Nerem RM. Effects of pulsatile flow on cultured vascular endothelial cell morphology. J Biomech Eng. 1991;113(2):123-131. https://doi.org/10.1115/1.2891226.
  56. Kaiser D, Freyberg MA, Friedl P. Lack of hemodynamic forces triggers apoptosis in vascular endothelial cells. Biochem Biophys Res Commun. 1997;231(3):586-590. https://doi.org/10.1006/bbrc.1997.6146.
  57. Kawai Y, Matsumoto Y, Ikeda Y, Watanabe K. Regulation of antithrombogenicity in endothelium by hemodynamic forces. Rinsho Byori. 1997;45(4):315-320.
  58. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991;88(11):4651-4655. https://doi.org/10.1073/pnas.88.11.4651.
  59. Kuchan MJ, Frangos JA. Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells. Am J Physiol. 1994;266(3 Pt 1):C628-636. https://doi.org/10.1152/ajpcell.1994.266.3.C628.
  60. Levesque M. Vascular endottielial cell proliferation in culture and the influence of flow. Biomaterials. 1990;11(9):702-707. https://doi.org/10.1016/0142-9612(90)90031-k.
  61. Malek AM, Jackman R, Rosenberg RD, Izumo S. Endothelial expression of thrombomodulin is reversibly regulated by fluid shear stress. Circ Res. 1994;74(5):852-860. https://doi.org/10.1161/01.res.74.5.852.
  62. Y. Ngai C. Vascular responses to shear stress: the involvement of mechanosensors in endothelial cells. Open Circ Vasc J. 2012;3(1):85-94. https://doi.org/10.2174/1877382601003010085.
  63. Noris M, Morigi M, Donadelli R, et al. Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions. Circ Res. 1995;76(4):536-543. https://doi.org/10.1161/01.res.76.4.536.
  64. Okahara K, Sun B, Kambayashi J. Upregulation of prostacyclin synthesis-related gene expression by shear stress in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 1998;18(12):1922-1926. https://doi.org/10.1161/01.atv.18.12.1922.
  65. Papaioannou TG, Stefanadis C. Vascular wall shear stress: basic principles and methods. Hellenic J Cardiol. 2005;46(1):9-15.
  66. Paszkowiak JJ, Dardik A. Arterial wall shear stress: observations from the bench to the bedside. Vasc Endovascular Surg. 2003;37(1):47-57. https://doi.org/10.1177/ 153857440303700107.
  67. Radomski MW, Palmer RM, Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci U S A. 1990;87(13):5193-5197. https://doi.org/10.1073/pnas.87.13.5193.
  68. Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol. 1986;250(6 Pt 2):H1145-1149. https://doi.org/10.1152/ajpheart.1986.250.6.H1145.
  69. Takada Y, Shinkai F, Kondo S, et al. Fluid shear stress increases the expression of thrombomodulin by cultured human endothelial cells. Biochem Biophys Res Commun. 1994;205(2):1345-1352. https://doi.org/10.1006/bbrc.1994.2813.
  70. Topper JN, Cai J, Falb D, Gimbrone MA, Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A. 1996;93(19):10417-10422. https://doi.org/10.1073/pnas.93.19.10417.
  71. Traub O, Berk BC. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol. 1998;18(5):677-685. https://doi.org/10.1161/01.atv.18.5.677.
  72. Vyalov S, Langille BL, Gotlieb AI. Decreased blood flow rate disrupts endothelial repair in vivo. Am J Pathol. 1996;149(6):2107-2118.
  73. Cheng C, Tempel D, van Haperen R, et al. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation. 2006;113(23):2744-2753. https://doi.org/10.1161/CIRCULATIONAHA.105.590018.
  74. Guo FX, Hu YW, Zheng L, Wang Q. Shear stress in autophagy and its possible mechanisms in the process of atherosclerosis. DNA Cell Biol. 2017;36(5):335-346. https://doi.org/10.1089/dna.2017.3649.
  75. Kuma A, Mizushima N. Physiological role of autophagy as an intracellular recycling system: with an emphasis on nutrient metabolism. Semin Cell Dev Biol. 2010;21(7):683-690. https://doi.org/10.1016/j.semcdb.2010.03.002.
  76. Mizushima N. Physiological functions of autophagy. Curr Top Microbiol Immunol. 2009;335:71-84. https://doi.org/10.1007/978-3-642-00302-8_3.
  77. Lavandero S, Troncoso R, Rothermel BA, et al. Cardiovascular autophagy: concepts, controversies, and perspectives. Autophagy. 2013;9(10):1455-1466. https://doi.org/10.4161/auto.25969.
  78. Lavandero S, Chiong M, Rothermel BA, Hill JA. Autophagy in cardiovascular biology. J Clin Invest. 2015;125(1):55-64. https://doi.org/10.1172/JCI73943.
  79. Yang Q, Li X, Li R, et al. Low shear stress inhibited endothelial cell autophagy through TET2 downregulation. Ann Biomed Eng. 2016;44(7):2218-2227. https://doi.org/10.1007/s10439-015-1491-4.
  80. Torisu K, Singh KK, Torisu T, et al. Intact endothelial autophagy is required to maintain vascular lipid homeostasis. Aging Cell. 2016;15(1):187-191. https://doi.org/10.1111/acel.12423.
  81. Park SK, La Salle DT, Cerbie J, et al. Elevated arterial shear rate increases indexes of endothelial cell autophagy and nitric oxide synthase activation in humans. Am J Physiol Heart Circ Physiol. 2019;316(1):H106-H112. https://doi.org/10.1152/ajpheart.00561.2018.
  82. Shesely EG, Maeda N, Kim HS, et al. Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1996;93(23):13176-13181. https://doi.org/10.1073/pnas.93.23.13176.
  83. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83(5):1774-1777. https://doi.org/10.1172/JCI114081.
  84. Bernatchez P, Sharma A, Bauer PM, et al. A noninhibitory mutant of the caveolin-1 scaffolding domain enhances eNOS-derived NO synthesis and vasodilation in mice. J Clin Invest. 2011;121(9):3747-3755. https://doi.org/10.1172/JCI44778.
  85. Trane AE, Pavlov D, Sharma A, et al. Deciphering the binding of caveolin-1 to client protein endothelial nitric-oxide synthase (eNOS): scaffolding subdomain identification, interaction modeling, and biological significance. J Biol Chem. 2014;289(19):13273-13283. https://doi.org/10.1074/jbc.M113.528695.

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2. Fig. 1. Chylomicron metabolism. Chylomicrons transport triglycerides from the intestine to the peripheral tissues: HDL — high density lipoprotein; CE — cholesteryl esters; АI, II, IV, V, СI, II, III, Е, B-48 — apolipoproteins; TG — triglycerides; LDL receptor — low density lipoprotein receptor; LRP — low density lipoprotein receptor-related protein [11]

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3. Fig. 2. Very low density lipoprotein metabolism: HDL — high density lipoprotein; LDL — low density lipoprotein; VLDL — very low density lipoprotein; TG — triglycerides; CE — cholesteryl esters; АI, II, IV, Е, СI, II, III, B100 — apolipoproteins; HTGL — hepatic triglyceride lipase; LDL receptor — low density lipoprotein receptor [11]

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4. Fig. 3. Low density lipoprotein metabolism: HDL — high density lipoprotein; LDL — low density lipoprotein; VLDL — very low density lipoprotein; E, C, B100 — apolipoproteins; HTGL — hepatic triglyceride lipase; LDL receptor — low density lipoprotein receptor [11]

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5. Fig. 4. High density lipoprotein metabolism: HDL — high density lipoprotein; VLDL — very low density lipoprotein; TG — triglycerides; АI, AII, Е, С — apolipoproteins; CE — cholesteryl esters; ABCA1 — ATP-binding cassette transporter A1; LCAT — lecithin cholesteryl-ester transferase [11]

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6. Fig. 5. Low density lipoprotein transport through the endothelium: LDL — low density lipoprotein; LDLR — LDL receptor; ALK1 — activin receptor-like kinase; SR-B1 — scavenger receptor B1 [32]

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7. Fig. 6. Caveola: schematic (left) and electron micrograph (right) [28]

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8. Fig. 7. Schematic representation of the shear stress patterns induced by the cast. On the right, straight segment of a mouse carotid artery without a cast, which has laminar blood flow (indicated by parallel arrows). Based on Doppler measurements, the average shear stress has been calculated as 15 N/m2. On the left, mouse carotid artery with the conical cast. Upstream from the cast, shear stress is relatively low (compared with the shear stress in the control vessel), 10 N/m2, caused by the flow-limiting stenosis induced by the cast. Within the cast, shear stress increases from relatively low (10 N/m2) to relatively high (25 N/m2) because of the tapered shape of the cast. Downstream from the cast, shear stress is oscillatory (~14 N/m2) [73]

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9. Fig. 8. Lowered shear stress and vortices with oscillatory shear stress induce atherosclerosis in mice fed on atherogenic Western diet [73]. Aortic arches and carotid arteries were stained with Oil red O for atherosclerotic lesions. White lines demarcate the position of the cast. Upstream from the cast is the lowered shear stress region, and downstream from the cast is the oscillatory shear stress region. Animals were instrumented with a cast 2 weeks after starting the diet. Next animals were humanely killed after 6 (a), 9 (b), or 12 (c–e) weeks of cast placement. No lesions were detected in the carotid arteries of either sham-operated mice (d) or animals instrumented with a nonconstrictive cast (e). Each of experimental mice groups consists of 6 to 8 animals

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