The interface of atherosclerosis and thrombosis: basic mechanisms

Occlusive vascular disease most often results from thrombosis superimposed on atherosclerotic plaque. Disruption of plaque exposes thrombogenic substances within the plaque to blood and may result in thrombotic occlusion of the affected vessel. Mural thrombi may be incorporated into plaque, enhancing the evolution of atherosclerotic lesions. inflammation plays a key role in the formation and complication of atherosclerosis. inflammatory mediators regulate processes that determine the composition of the plaque's fibrous cap, a structure that separates blood from the thrombogenic lipid core. Several inflammatory mediators control the release of metalloproteinases (enzymes that break down cap constituents) from smooth muscle cells, macrophages and other cells within plaque. inflammatory mediators also control the production of connective tissue matrix by cells in the plaque. Factors involved in coagulation, such as thrombin, can regulate non-thrombotic functions of vascular wall cells such as smooth muscle proliferation or cytokine release. The many mechanisms involved in arterial occlusive disease present numerous points at which intervention with pharmacologic agents may prove effective in lowering the risk of acute arterial thrombotic complications.

[1]  T. Ogihara,et al.  Possible participation of Fas-mediated apoptosis in the mechanism of atherosclerosis. , 1997, Gerontology.

[2]  B. Baxter,et al.  Macrophage Products Inhibit Human Aortic Smooth Muscle Cell Proliferation and Alter 1α(I) Procollagen Expression , 1997, Annals of vascular surgery.

[3]  Richard T. Lee,et al.  Macrophages and atherosclerotic plaque stability , 1996, Current opinion in lipidology.

[4]  V. Fuster,et al.  Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. , 1997, Circulation.

[5]  P. Carmeliet,et al.  Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation , 1997, Nature Genetics.

[6]  P. Libby,et al.  Apoptosis of Vascular Smooth Muscle Cells Induced by In Vitro Stimulation With Interferon-γ, Tumor Necrosis Factor–α, and Interleukin-1β , 1996 .

[7]  M J Davies,et al.  Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. , 1996, Circulation.

[8]  R. Poston,et al.  Localized adhesion of monocytes to human atherosclerotic plaques demonstrated in vitro: implications for atherogenesis. , 1996, The American journal of pathology.

[9]  A. Gown,et al.  Various cell types in human atherosclerotic lesions express ICAM-1. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3. , 1992, The American journal of pathology.

[10]  P. Libby,et al.  Enhanced Expression of Vascular Matrix Metalloproteinases Induced In Vitro by Cytokines and in Regions of Human Atherosclerotic Lesions a , 1994, Annals of the New York Academy of Sciences.

[11]  R. Virmani,et al.  The association of mast cells and atherosclerosis: a morphologic study of early atherosclerotic lesions in young people. , 1994, Human pathology.

[12]  P. Libby,et al.  Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[13]  Michael Loran Dustin,et al.  Intercellular adhesion molecule-1 dimerization and its consequences for adhesion mediated by lymphocyte function associated-1 , 1995, The Journal of experimental medicine.

[14]  P. Libby,et al.  Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Alan D. Lopez,et al.  Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study , 1997, The Lancet.

[16]  L. Stanton,et al.  CD36 is a receptor for oxidized low density lipoprotein. , 1993, The Journal of biological chemistry.

[17]  A. Tall,et al.  IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. , 1997, The Journal of clinical investigation.

[18]  T. Warner.  Influence of endothelial mediators on the vascular smooth muscle and circulating platelets and blood cells. , 1996, International angiology : a journal of the International Union of Angiology.

[19]  T. Kodama,et al.  Purification and characterization of a bovine acetyl low density lipoprotein receptor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[20]  P. Lesnik,et al.  Phagocytic activation induces formation of platelet-activating factor in human monocyte-derived macrophages and in macrophage-derived foam cells. Relevance to the inflammatory reaction in atherogenesis. , 1996, European journal of biochemistry.

[21]  J. Dayer,et al.  IL-10 inhibits metalloproteinase and stimulates TIMP-1 production in human mononuclear phagocytes. , 1995, The Journal of clinical investigation.

[22]  Samin K. Sharma,et al.  Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes. , 1996, Circulation.

[23]  E. Edelman,et al.  Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels , 1997, Nature.

[24]  D. Woolley,et al.  MAST CELL DISTRIBUTION, ACTIVATION, AND PHENOTYPE IN ATHEROSCLEROTIC LESIONS OF HUMAN CAROTID ARTERIES , 1997, The Journal of pathology.

[25]  P. Libby,et al.  An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[26]  P. Kovanen,et al.  Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha. , 1996, Circulation.

[27]  G. Zimmerman,et al.  Platelet-activating factor mediates procoagulant activity on the surface of endothelial cells by promoting leukocyte adhesion. , 1995, Seminars in cell biology.

[28]  P. Libby,et al.  Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Libby,et al.  Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture? , 1997, Circulation research.

[30]  P. Reitsma,et al.  Tissue Factor Expression during Monocyte-Macrophage Differentiation , 1997, Thrombosis and Haemostasis.

[31]  S. Pizzo,et al.  Activated alpha 2-macroglobulin promotes mitogenesis in rat vascular smooth muscle cells by a mechanism that is independent of growth-factor-carrier activity. , 1995, European journal of biochemistry.

[32]  P. Kovanen,et al.  Mast cells accompany microvessels in human coronary atheromas: implications for intimal neovascularization and hemorrhage. , 1996, Atherosclerosis.

[33]  P. Libby,et al.  Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. , 1997, Circulation.

[34]  J. Auwerx,et al.  Transcriptional activation of the lipoprotein lipase and apolipoprotein E genes accompanies differentiation in some human macrophage-like cell lines. , 1988, Biochemistry.

[35]  P. Kovanen,et al.  TNF-alpha and IL-1beta selectively induce expression of 92-kDa gelatinase by human macrophages. , 1996, Journal of immunology.

[36]  P. Kiener,et al.  Activation of human monocytes through CD40 induces matrix metalloproteinases. , 1996, Journal of immunology.

[37]  Kathleen M. Smith,et al.  Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Davies,et al.  The expression of the adhesion molecules ICAM‐1, VCAM‐1, PECAM, and E‐selectin in human atherosclerosis , 1993, The Journal of pathology.

[39]  G. Evan,et al.  Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. , 1995, The Journal of clinical investigation.

[40]  J. Rapp.  Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF , 1993 .

[41]  Helen H. Hobbs,et al.  Identification of Scavenger Receptor SR-BI as a High Density Lipoprotein Receptor , 1996, Science.

[42]  G. Zimmerman,et al.  Platelet-activating factor acetylhydrolase increases during macrophage differentiation. A novel mechanism that regulates accumulation of platelet-activating factor. , 1989, The Journal of biological chemistry.

[43]  K E Norman,et al.  Leukocyte rolling in vivo is mediated by P-selectin glycoprotein ligand-1. , 1995, Blood.

[44]  D. Steinberg,et al.  The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[45]  M. Cybulsky,et al.  Advanced Glycation Endproducts Promote Adhesion Molecule (VCAM-1, ICAM-1) Expression and Atheroma Formation in Normal Rabbits , 1995, Molecular medicine.

[46]  P. Libby,et al.  The unstable atheroma. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[47]  D. Harrison,et al.  Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. , 1996, The Journal of clinical investigation.

[48]  M J Davies,et al.  Relation of plaque lipid composition and morphology to the stability of human aortic plaques. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[49]  G. Assmann,et al.  Association of Variables of Coagulation, Fibrinolysis and Acute-phase with Atherosclerosis in Coronary and Peripheral Arteries and those Arteries Supplying the Brain , 1995, Thrombosis and Haemostasis.

[50]  J. Coucher,et al.  Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. , 1992, The American journal of pathology.

[51]  T. Drake,et al.  Induction of P-selectin by oxidized lipoproteins. Separate effects on synthesis and surface expression. , 1997, Circulation research.

[52]  P. Libby,et al.  Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme. , 1995, The American journal of pathology.

[53]  P. Kovanen,et al.  Chymase in exocytosed rat mast cell granules effectively proteolyzes apolipoprotein AI-containing lipoproteins, so reducing the cholesterol efflux-inducing ability of serum and aortic intimal fluid. , 1996, The Journal of clinical investigation.

[54]  F. Rickles,et al.  The role of human T cells (and T cell products) for monocyte tissue factor generation. , 1980, Journal of immunology.

[55]  M. Cybulsky,et al.  Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. , 1991, Science.

[56]  P. Libby,et al.  Thrombin promotes activation of matrix metalloproteinase-2 produced by cultured vascular smooth muscle cells. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[57]  D. Hajjar,et al.  Lipoprotein Trafficking in Vascular Cells , 1997, The Journal of Biological Chemistry.

[58]  P. Libby,et al.  Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.