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Vascular Endothelium and Atherosclerosis

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The Vascular Endothelium II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 176/II))

Abstract

Atherosclerosis depends critically on altered behavior of the intrinsic cells of the artery wall, the endothelial cells and smooth muscle cells, and inflammatory leukocytes that join them in the arterial intima during the atherogenic process. The homeostatic properties of the normal endothelium contribute importantly to maintenance of aspects of arterial health including the appropriate regulation of blood flow, a basal anti-inflammatory state, promotion of fibrinolysis while opposing blood coagulation, and control of the balance of cellular proliferation and death. Alterations in these endothelial homeostatic mechanisms contribute critically to atherogenesis, the progression of this disease, and ist complications. Recent advances have highlighted novel molecular mechanisms that regulate the atheroprotective functions of normal endothelial cells that go awry during atherogenesis. Therapeutic strategies that alter the course of atherosclerosis may act by combating endothelial dysfunction.

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References

  • Aikawa M, Libby P (2004) The vulnerable atherosclerotic plaque: pathogenesis and therapeutic approach. Cardiovasc Pathol 13:125–138

    Article  PubMed  Google Scholar 

  • Aikawa M, Sugiyama S, Hill C, Voglic S, Rabkin E, Fukumoto Y, Schoen F, Witztum JL, Libby P (2002) Lipid lowering reduces oxidative stress and endothelial cell activation in rabbit atheroma. Circulation 106:1390–1396

    Article  PubMed  CAS  Google Scholar 

  • Altschul R (1954) Endothelium; its development, morphology, function, and pathology. Macmillan, New York

    Google Scholar 

  • Barger A, Beeuwkes IR, Lainey L, Silverman K (1984) Hypothesis: vasa vasorum and neovascularization of human coronary arteries. N Engl J Med 310:175–177

    Article  PubMed  CAS  Google Scholar 

  • Berliner JA, Watson AD (2005) A role for oxidized phospholipids in atherosclerosis. N Engl J Med 353:9–11

    Article  PubMed  CAS  Google Scholar 

  • Boisvert WA, Curtiss LK, Terkeltaub RA (2000) Interleukin-8 and its receptor CXCR2 in atherosclerosis. Immunol Res 21:129–137

    Article  PubMed  CAS  Google Scholar 

  • Brogi E, Winkles J, Underwood R, Clinton S, Alberts G, Libby P (1993) Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and non-atherosclerotic arteries: association of acidic FGF with plaque microvessels and macrophages. J Clin Invest 92:2408–2418

    PubMed  CAS  Google Scholar 

  • Cybulsky MI, Gimbrone MA Jr (1991) Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251:788–791

    Article  PubMed  CAS  Google Scholar 

  • Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS (2001) A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 107:1255–1262

    PubMed  CAS  Google Scholar 

  • Davies MJ (1996) Stability and instability: the two faces of coronary atherosclerosis. The Paul Dudley White Lecture, 1995. Circulation 94:2013–2020

    PubMed  CAS  Google Scholar 

  • De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MJ, Libby P (1995) The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 14:1829–1836

    Google Scholar 

  • Dekker RJ, Von Soest S, Fontijn RD, Salamanca S, de Groot PG, VanBavel E, Pannekoek H, Horrevoets AJG (2002) Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2). Blood 100:1689–1698

    Article  PubMed  CAS  Google Scholar 

  • Delerive P, De Bosscher K, Besnard S, Vanden Berghe W, Peters JM, Gonzalez FJ, Fruchart JC, Tedgui A, Haegeman G, Staels B (1999) Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 274:32048–32054

    Article  PubMed  CAS  Google Scholar 

  • Dollery CM, Libby P (2006) Atherosclerosis and proteinase activation. Cardiovasc Res 69:625–635

    Article  PubMed  CAS  Google Scholar 

  • Dollery CM, Owen CA, Sukhova GK, Krettek A, Shapiro SD, Libby P (2003) Neutrophil elastase in human atherosclerotic plaques: production by macrophages. Circulation 107:2829–2836

    Article  PubMed  CAS  Google Scholar 

  • Faggiotto A, Ross R, Harker L (1984) Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis 4:323–340

    PubMed  CAS  Google Scholar 

  • Gimbrone MA Jr (1981) Vascular endothelium and atherosclerosis. In: Moore S (ed) Vascular injury and atherosclerosis. Marcel Dekker, New York, pp 25–52

    Google Scholar 

  • Gimbrone MA Jr, Cotran RS, Folkman J (1974) Human vascular endothelial cells in culture. Growth and DNA synthesis. J Cell Biol 60:673–684

    Article  PubMed  CAS  Google Scholar 

  • Griendling KK, Harrison DG (2001) Out, damned dot: studies of the NADPH oxidase in atherosclerosis. J Clin Invest 108:1423–1424

    Article  PubMed  CAS  Google Scholar 

  • Gu L, Okada Y, Clinton S, Gerard C, Sukhova G, Libby P, Rollins B (1998) Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low-density lipoprotein-deficient mice. Mol Cell 2:275–281

    Article  PubMed  CAS  Google Scholar 

  • Haley KJ, Lilly CM, Yang JH, Feng Y, Kennedy SP, Turi TG, Thompson JF, Sukhova GK, Libby P, Lee RT (2000) Overexpression of eotaxin and the CCR3 receptor in human atherosclerosis: using genomic technology to identify a potential novel pathway of vascular inflammation. Circulation 102:2185–2189

    PubMed  CAS  Google Scholar 

  • Hazen SL, Hsu FF, Gaut JP, Crowley JR, Heinecke JW (1999) Modification of proteins and lipids by myeloperoxidase. Methods Enzymol 300:88–105

    PubMed  CAS  Google Scholar 

  • Heinecke JW (2003) Oxidative stress: new approaches to diagnosis and prognosis in atherosclerosis. Am J Cardiol 91:12A–16A

    Article  PubMed  CAS  Google Scholar 

  • Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, Kroczek RA (1998) CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391:591–594

    Article  PubMed  CAS  Google Scholar 

  • Jaffe EA, Nachmann RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. J Clin Invest 52:2745–2756

    PubMed  CAS  Google Scholar 

  • Jain MK, Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4:977–987

    Article  PubMed  CAS  Google Scholar 

  • Joris T, Nunnari JJ, Krolikowski FJ, Majno G (1983) Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol 113:341–358

    PubMed  CAS  Google Scholar 

  • Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M, Kutys R, Narula J, Finn AV, Virmani R (2003) Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 349:2316–2325

    Article  PubMed  CAS  Google Scholar 

  • Krauss RM (2005) Nutrition and cardiovascular disease. In: Zipes DP, Libby P, Bonow RO, Braunwald E (eds) Braunwald’s heart disease: a textbook of cardiovascular medicine, vol 1. Elsevier Saunders, Philadelphia, pp 1047–1056

    Google Scholar 

  • Kumar A, Lin Z, Senbanerjee S, Jain MK (2005) Tumor necrosis factor alpha-mediated reduction of KLF2 is due to inhibition of MEF2 by NF-kappaB and histone deacetylases. Mol Cell Biol 25:5893–5903

    Article  PubMed  CAS  Google Scholar 

  • Lesnik P, Haskell CA, Charo IF (2003) Decreased atherosclerosis in CX3CR1-/-mice reveals a role for fractalkine in atherogenesis. J Clin Invest 111:333–340

    Article  PubMed  CAS  Google Scholar 

  • Li H, Cybulsky MI, Gimbrone MA Jr, Libby P (1993) An atherogenic diet rapidly induces VCAM-1, a cytokine regulatable mononuclear leukocyte adhesion molecule, in rabbit endothelium. Arterioscler Thromb 13:197–204

    PubMed  Google Scholar 

  • Libby P (1987) The active roles of cells of the blood vessel wall in health and disease. Mol Aspects Med 9:499–567

    Article  PubMed  CAS  Google Scholar 

  • Libby P (1990) Inflammatory and immune mechanisms in atherogenesis. In: Leaf A, Weber P (eds) Atherosclerosis reviews, vol 21. Raven Press, New York, pp 79–89

    Google Scholar 

  • Libby P, Aikawa M (2002) Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med 8:1257–1262

    Article  PubMed  CAS  Google Scholar 

  • Libby P, Simon DI (2001) Inflammation and thrombosis: the clot thickens. Circulation 103:1718–1720

    PubMed  CAS  Google Scholar 

  • Libby P, Theroux P (2005) Pathophysiology of coronary artery disease. Circulation 111:3481–3488

    Article  PubMed  Google Scholar 

  • Libby P, Egan D, Skarlatos S (1997) Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. Circulation 96:4095–4103

    PubMed  CAS  Google Scholar 

  • Libby P, Ganz P, Schoen FJ, Lee RT (2000) The vascular biology of the acute coronary Syndromes. In: Topol EJ (ed) Acute coronary syndromes. Marcel Dekker, New York, pp 33–57

    Google Scholar 

  • Lin Z, Kumar A, Senbanerjee S, Staniszewski K, Parmar K, Vaughan DE, Gimbrone MA Jr, Balasubramanian V, Garcia-Cardena G, Jain MK (2005) Kruppel-like factor 2 (KLF2) regulates endothelial thrombotic function. Circ Res 96:e48–e57

    Article  PubMed  CAS  Google Scholar 

  • Marx N, Sukhova GK, Collins T, Libby P, Plutzky J (1999) PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 99:3125–3131

    PubMed  CAS  Google Scholar 

  • Marx N, Libby P, Plutzky J (2001) Peroxisome proliferator-activated receptors (PPARs) and their role in the vessel wall: possible mediators of cardiovascular risk? J Cardiovasc Risk 8:203–210

    Article  PubMed  CAS  Google Scholar 

  • Matsushita K, Morrell CN, Cambien B, Yang SX, Yamakuchi M, Bao C, Hara MR, Quick RA, Cao W, O’Rourke B, Lowenstein JM, Pevsner J, Wagner DD, Lowenstein CJ (2003) Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell 115:139–150

    Article  PubMed  CAS  Google Scholar 

  • Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J (1999) Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99:1726–1732

    PubMed  CAS  Google Scholar 

  • Nagel T, Resnick N, Dewey CF Jr, Gimbrone MA Jr (1999) Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arterioscler Thromb Vasc Biol 19:1825–1834

    PubMed  CAS  Google Scholar 

  • O’Brien K, Allen M, McDonald T, Chait A, Harlan J, Fishbein D, McCarty J, Ferguson M, Hudkins K, Benjamin C, Lobb R, Alpers C (1993) Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques: implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest 92:945–951

    Article  PubMed  CAS  Google Scholar 

  • Parmar KM, Nambudiri V, Dai G, Larman HB, Gimbrone MA Jr, Garcia-Cardena G (2005) Statins exert endothelial atheroprotective effects via the KLF2 transcription factor. J Biol Chem 280:26714–26719

    Article  PubMed  CAS  Google Scholar 

  • Parmar KM, Larman HB, Dai G, Zhang Y, Wang ET, Moorthy SN, Kratz JR, Lin Z, Jain MK, Gimbrone MA, Garcia-Cardena G (2006) Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J Clin Invest 116:49–58

    Article  PubMed  CAS  Google Scholar 

  • Peng HB, Libby P, Liao JK (1995) Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. J Biol Chem 270:14214–14219

    Article  PubMed  CAS  Google Scholar 

  • Peters W, Charo IF (2001) Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis: lessons from knockout mice. Curr Opin Lipidol 12:175–180

    Article  PubMed  CAS  Google Scholar 

  • Poole JCF, Florey HW (1958) Changes in the endothelium of the aorta and the behavior of macrophages in experimental atheroma of rabbits. J Pathol Bacteriol 75:245–253

    Article  PubMed  CAS  Google Scholar 

  • Rajavashisth T, Qiao JH, Tripathi S, Tripathi J, Mishra N, Hua M, Wang XP, Loussararian A, Clinton S, Libby P, Lusis A (1998) Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest 101:2702–2710

    PubMed  CAS  Google Scholar 

  • Rajavashisth TB, Liao JK, Galis ZS, Tripathi S, Laufs U, Tripathi J, Chai NN, Xu XP, Jovinge S, Shah PK, Libby P (1999) Inflammatory cytokines and oxidized low density lipoproteins increase endothelial cell expression of membrane type 1-matrixmetalloproteinase. J Biol Chem 274:11924–11929

    Article  PubMed  CAS  Google Scholar 

  • Rikitake Y, Liao JK (2005) Rho GTPases, statins, and nitric oxide. Circ Res 97:1232–1235

    Article  PubMed  CAS  Google Scholar 

  • Ross R, Glomset JA (1976) The pathogenesis of atherosclerosis (part I). N Engl J Med 295:369–377

    Article  PubMed  CAS  Google Scholar 

  • Schonbeck U, Libby P (2004) Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation 109:II18–II26

    Article  PubMed  CAS  Google Scholar 

  • Sen-Banerjee S, Mir S, Lin Z, Hamik A, Atkins GB, Das H, Banerjee P, Kumar A, Jain MK (2005) Kruppel-like factor 2 as a novel mediator of statin effects in endothelial cells. Circulation 112:720–726

    Article  PubMed  CAS  Google Scholar 

  • SenBanerjee S, Lin Z, Atkins GB, Greif DM, Rao RM, Kumar A, Feinberg MW, Chen Z, Simon DI, Luscinskas FW, Michel TM, Gimbrone MA Jr, Garcia-Cardena G, Jain MK (2004) KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med 199:1305–1315

    Article  PubMed  CAS  Google Scholar 

  • Shaw G (1911) The doctor’s dilemma. Penguin Books, Baltimore

    Google Scholar 

  • Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M (1995) Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci U S A 92:8264–8268

    Article  PubMed  CAS  Google Scholar 

  • Sugiyama S, Okada Y, Sukhova GK, Virmani R, Heinecke JW, Libby P (2001) Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol 158:879–891

    PubMed  CAS  Google Scholar 

  • Sugiyama S, Kugiyama K, Aikawa M, Nakamura S, Ogawa H, Libby P (2004) Hypochlorous acid, a macrophage product, induces endothelial apoptosis and tissue factor expression: involvement of myeloperoxidase-mediated oxidant in plaque erosion and thrombogenesis. Arterioscler Thromb Vasc Biol 24:1309–1314

    Article  PubMed  CAS  Google Scholar 

  • Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437:426–431

    Article  PubMed  CAS  Google Scholar 

  • van der Wal AC, Becker AE, van der Loos CM, Das PK (1994) Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 89:36–44

    PubMed  Google Scholar 

  • Vaughan DE (2005) PAI-1 and atherothrombosis. J Thromb Haemost 3:1879–1883

    Article  PubMed  CAS  Google Scholar 

  • Virmani R, Burke AP, Farb A, Kolodgie FD (2002) Pathology of the unstable plaque. Prog Cardiovasc Dis 44:349–356

    Article  PubMed  Google Scholar 

  • Wagner DD (2005) New links between inflammation and thrombosis. Arterioscler Thromb Vasc Biol 25:1321–1324

    Article  PubMed  CAS  Google Scholar 

  • Yamawaki H, Pan S, Lee RT, Berk BC (2005) Fluid shear stress inhibits vascular inflammation by decreasing thioredoxin-interacting protein in endothelial cells. J Clin Invest 115:733–738

    Article  PubMed  CAS  Google Scholar 

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Libby, P., Aikawa, M., Jain, M.K. (2006). Vascular Endothelium and Atherosclerosis. In: Moncada, S., Higgs, A. (eds) The Vascular Endothelium II. Handbook of Experimental Pharmacology, vol 176/II. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-36028-X_9

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