Inflammation in Atherosclerosis

Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances.

[1]  P. Libby,et al.  Extramedullary Hematopoiesis Generates Ly-6Chigh Monocytes That Infiltrate Atherosclerotic Lesions , 2012, Circulation.

[2]  P. Libby,et al.  Selective Inhibition of Matrix Metalloproteinase-13 Increases Collagen Content of Established Mouse Atherosclerosis , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[3]  P. Libby,et al.  Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). , 2011, American heart journal.

[4]  P. Libby,et al.  IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-/- mice. , 2011, The Journal of clinical investigation.

[5]  P. Libby,et al.  Progress and challenges in translating the biology of atherosclerosis , 2011, Nature.

[6]  C. Uyttenhove,et al.  B cell depletion reduces the development of atherosclerosis in mice , 2010, The Journal of experimental medicine.

[7]  J. Danesh,et al.  C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis , 2010, The Lancet.

[8]  I. Tabas Macrophage death and defective inflammation resolution in atherosclerosis , 2010, Nature Reviews Immunology.

[9]  G. Hansson,et al.  The discovery of cellular immunity in the atherosclerotic plaque. , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[10]  P. Libby,et al.  Kruppel-like Factor KLF10 Targets Transforming Growth Factor-β1 to Regulate CD4+CD25− T Cells and T Regulatory Cells* , 2009, The Journal of Biological Chemistry.

[11]  P. Ridker Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT) , 2009, Journal of thrombosis and haemostasis : JTH.

[12]  G. Hansson,et al.  Vaccination against atherosclerosis? Induction of atheroprotective immunity , 2009, Seminars in Immunopathology.

[13]  Børge G Nordestgaard,et al.  Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial , 2009, The Lancet.

[14]  P. Libby,et al.  Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. , 2008, The New England journal of medicine.

[15]  J. Witztum,et al.  Natural antibodies in murine atherosclerosis. , 2008, Current drug targets.

[16]  P. Libby,et al.  Matrix Metalloproteinase-14 Deficiency in Bone Marrow–Derived Cells Promotes Collagen Accumulation in Mouse Atherosclerotic Plaques , 2008, Circulation.

[17]  P. Libby,et al.  Mast cells promote atherosclerosis by releasing proinflammatory cytokines , 2007, Nature Medicine.

[18]  A. Zernecke,et al.  Perivascular Mast Cells Promote Atherogenesis and Induce Plaque Destabilization in Apolipoprotein E–Deficient Mice , 2007, Circulation.

[19]  N. Cook,et al.  Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. , 2007, JAMA.

[20]  F. Tacke,et al.  Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. , 2007, The Journal of clinical investigation.

[21]  P. Libby,et al.  Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. , 2007, The Journal of clinical investigation.

[22]  R. Flavell,et al.  Natural regulatory T cells control the development of atherosclerosis in mice , 2006, Nature Medicine.

[23]  Elena Aikawa,et al.  Matrix Metalloproteinase-13/Collagenase-3 Deletion Promotes Collagen Accumulation and Organization in Mouse Atherosclerotic Plaques , 2005, Circulation.

[24]  P. Libby,et al.  Genetically Determined Resistance to Collagenase Action Augments Interstitial Collagen Accumulation in Atherosclerotic Plaques , 2004, Circulation.

[25]  M. Nieminen,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[26]  G. Hansson,et al.  Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. , 2002, The Journal of clinical investigation.

[27]  P. Libby,et al.  Inflammation and Atherosclerosis , 2002, Circulation.

[28]  R. Virmani,et al.  Pathology of the unstable plaque. , 2002, Progress in cardiovascular diseases.

[29]  P. Libby,et al.  Expression of Neutrophil Collagenase (Matrix Metalloproteinase-8) in Human Atheroma: A Novel Collagenolytic Pathway Suggested by Transcriptional Profiling , 2001, Circulation.

[30]  Peter Libby,et al.  Current Concepts of the Pathogenesis of the Acute Coronary Syndromes , 2001, Circulation.

[31]  Paul M. Ridker,et al.  Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. , 2001, The New England journal of medicine.

[32]  M. Cybulsky,et al.  A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. , 2001, The Journal of clinical investigation.

[33]  P. Libby,et al.  Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. , 2001, The American journal of pathology.

[34]  M. Cybulsky,et al.  NF-κB: pivotal mediator or innocent bystander in atherogenesis? , 2001 .

[35]  B. Jude,et al.  PPARα Agonists Inhibit Tissue Factor Expression in Human Monocytes and Macrophages , 2001 .

[36]  P. Libby,et al.  An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro , 2001, Circulation.

[37]  P. Libby,et al.  PPAR&agr; Activators Inhibit Tissue Factor Expression and Activity in Human Monocytes , 2001, Circulation.

[38]  Xinghua Zhou,et al.  Transfer of CD4+ T Cells Aggravates Atherosclerosis in Immunodeficient Apolipoprotein E Knockout Mice , 2000, Circulation.

[39]  Richard T. Lee,et al.  Overexpression of Eotaxin and the CCR3 Receptor in Human Atherosclerosis: Using Genomic Technology to Identify a Potential Novel Pathway of Vascular Inflammation , 2000, Circulation.

[40]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[41]  Frank J. Gonzalez,et al.  Peroxisome Proliferator-activated Receptor α Negatively Regulates the Vascular Inflammatory Gene Response by Negative Cross-talk with Transcription Factors NF-κB and AP-1* , 1999, The Journal of Biological Chemistry.

[42]  P. Libby,et al.  Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. , 1999, The Journal of clinical investigation.

[43]  T Suzuki,et al.  Process of progression of coronary artery lesions from mild or moderate stenosis to moderate or severe stenosis: A study based on four serial coronary arteriograms per year. , 1999, Circulation.

[44]  P. Libby,et al.  Angiotensin induces inflammatory activation of human vascular smooth muscle cells. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[45]  P. Libby,et al.  PPARα Activators Inhibit Cytokine-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells , 1999 .

[46]  P. Libby,et al.  Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. , 1999, Circulation.

[47]  P. Libby,et al.  Inflammatory Cytokines and Oxidized Low Density Lipoproteins Increase Endothelial Cell Expression of Membrane Type 1-Matrix Metalloproteinase* , 1999, The Journal of Biological Chemistry.

[48]  M A Konerding,et al.  Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. , 1999, Circulation.

[49]  A. Schmidt,et al.  Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. , 1999, Circulation research.

[50]  A. Becker,et al.  Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization? , 1999, Cardiovascular research.

[51]  M. Gimbrone,et al.  Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype. , 1999, Molecular medicine today.

[52]  G. Fonarow,et al.  High density associated enzymes: their role in vascular biology. , 1998, Current opinion in lipidology.

[53]  M. Pfeffer,et al.  Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. , 1998, Circulation.

[54]  I. Charo,et al.  Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis , 1998, Nature.

[55]  P. Libby,et al.  Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. , 1998, Molecular cell.

[56]  R. Hynes,et al.  The combined role of P- and E-selectins in atherosclerosis. , 1998, The Journal of clinical investigation.

[57]  M. Kuzuya,et al.  Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[58]  P. Libby,et al.  Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice. , 1998, The Journal of clinical investigation.

[59]  R. Terkeltaub,et al.  A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. , 1998, The Journal of clinical investigation.

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

[61]  P. Libby,et al.  Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts. , 1997, The Journal of clinical investigation.

[62]  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.

[63]  Alan D. Lopez,et al.  Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study , 1997, The Lancet.

[64]  P. Libby,et al.  Role of macrophage colony-stimulating factor in atherosclerosis: studies of osteopetrotic mice. , 1997, The American journal of pathology.

[65]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[66]  T. Mayadas,et al.  Absence of P-selectin delays fatty streak formation in mice. , 1997, The Journal of clinical investigation.

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

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

[69]  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 .

[70]  P. Libby,et al.  Components of the protein fraction of oxidized low density lipoprotein stimulate interleukin-1 alpha production by rabbit arterial macrophage-derived foam cells. , 1995, Journal of lipid research.

[71]  T. Paavonen,et al.  Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. , 1995, Circulation.

[72]  Michael Ginsberg,et al.  Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

[74]  P. Libby,et al.  Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. , 1995, The Journal of clinical investigation.

[75]  P. Libby Molecular bases of the acute coronary syndromes. , 1995, Circulation.

[76]  P. Libby,et al.  Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. , 1994, The Journal of clinical investigation.

[77]  A. Rebuzzi,et al.  The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. , 1994, The New England journal of medicine.

[78]  P. Libby,et al.  Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages. , 1993, The Journal of clinical investigation.

[79]  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.

[80]  P. Libby,et al.  Increased apolipoprotein E and c-fms gene expression without elevated interleukin 1 or 6 mRNA levels indicates selective activation of macrophage functions in advanced human atheroma. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[81]  P. Libby,et al.  Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. , 1992, The American journal of pathology.

[82]  V. Ord,et al.  Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans. , 1992, The American journal of pathology.

[83]  P. Libby,et al.  Cytokines as mediators of vascular pathology. , 1992, Nouvelle revue francaise d'hematologie.

[84]  P. Libby,et al.  Human coronary transplantation-associated arteriosclerosis. Evidence for a chronic immune reaction to activated graft endothelial cells. , 1991, The American journal of pathology.

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

[86]  W. Weintraub,et al.  Elevation of C-reactive protein in "active" coronary artery disease. , 1990, The American journal of cardiology.

[87]  P. Libby,et al.  Functions of vascular wall cells related to development of transplantation-associated coronary arteriosclerosis. , 1989, Transplantation proceedings.

[88]  R. Detrano,et al.  The dynamics of progression of coronary atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. , 1989, American heart journal.

[89]  R. Cotran,et al.  Identification of an inducible endothelial-leukocyte adhesion molecule. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[90]  P. Libby,et al.  Inducible interleukin-1 gene expression in human vascular smooth muscle cells. , 1986, The Journal of clinical investigation.

[91]  P. Libby,et al.  Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. , 1986, The American journal of pathology.

[92]  G. Bondjers,et al.  Regional Accumulations of T Cells, Macrophages, and Smooth Muscle Cells in the Human Atherosclerotic Plaque , 1986, Arteriosclerosis.

[93]  H. Waldmann,et al.  Identification of macrophages and smooth muscle cells in human atherosclerosis using monoclonal antibodies , 1985, The Journal of pathology.

[94]  R. Ross,et al.  Studies of Hypercholesterolemia in the Nonhuman Primate: I. Changes that Lead to Fatty Streak Formation , 1984, Arteriosclerosis.

[95]  M. Karnovsky Metchnikoff in Messina: a century of studies on phagocytosis. , 1981, The New England journal of medicine.

[96]  R. Ross,et al.  Hyperlipidemia and atherosclerosis. , 1976, Science.

[97]  R. Ross,et al.  The pathogenesis of atherosclerosis (second of two parts). , 1976, The New England journal of medicine.

[98]  R. Ross,et al.  The pathogenesis of atherosclerosis (first of two parts). , 1976, The New England journal of medicine.

[99]  H. Florey,et al.  Changes in the endothelium of the aorta and the behaviour of macrophages in experimental atheroma of rabbits. , 1958, The Journal of pathology and bacteriology.