Progress in CardiologyInflammation and coronary artery disease
Section snippets
Inflammation in the initiation and progression of atherosclerosis
The normal endothelium has anti-inflammatory, antithrombotic, and vasodilatory properties for maintenance of blood flow while preventing thrombosis and leukocyte diapedesis. In the presence of proatherogenic factors, loss of these protective properties can occur, leading to endothelial dysfunction. Reduced nitric oxide bioavailability, a key molecule constitutively produced by healthy endothelium, can lead to impaired endothelial-dependent vasodilatation. It also permits activation of
Inflammation in plaque disruption and thrombotic complications
Exposure of the highly thrombogenic macrophage tissue factor, von Willebrand factor, and subendothelial collagen within the plaque core to circulating blood can trigger the coagulation cascade and platelet aggregation, leading rapidly to arterial thrombosis that characterizes acute coronary syndromes.17 The integrity of the fibrous cap is therefore considered pivotal in maintaining plaque stability. Formation and maintenance of the endothelialized fibrous cap can be regarded as smooth
Triggers and amplifiers of inflammation
The initial triggers for the inflammatory cascade leading to initiation and progression of atherosclerosis are not entirely clear. However, current evidence supports the role of the traditional cardiovascular risk factors and, to a lesser degree, novel risk factors such as infectious agents (Table I). Oxidized LDL and angiotensin II, a vasoconstrictor associated with hypertension, have been shown to increase the expression of vascular cell adhesion molecule-1 and MCP-1.3, 31, 32 The metabolic
Innate and adaptive immunity in atherosclerosis
The leukocyte composition in plaques suggests that atherosclerosis is mediated by macrophages and T lymphocytes, which are typically recruited during chronic inflammation and cell-mediated immunity, and implicates both innate and adaptive immunity (Table II). Macrophages by far outnumber other inflammatory cells in the plaque. Both helper T cells (Th) and cytotoxic T cells are also present, constituting 10% to 20% of the cell population in advanced plaques. Of these, activated Th1 cells and Th1
Clinical implications
Progress in our understanding of the inflammatory pathways in coronary artery disease provides a mechanistic framework for understanding the clinical benefits of existing therapies.17 For instance, the hydroxymethylglutaryl coenzyme-A inhibitors or statins have been shown in multiple primary and secondary prevention trials to be effective in reducing cardiovascular events. Until recently, this benefit was attributed to their cholesterol-lowering properties. However, it is now recognized that
References (55)
- et al.
Cellular adhesion molecules and atherogenesis
Am J Cardiol
(1999) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm
Cell
(1994)- et al.
Chemokines: leucocyte recruitment and activation cytokines
Lancet
(1997) - et al.
Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified LDL leading to lipid loading in macrophages
J Biol Chem
(2002) - et al.
Hypochlorous acid oxygenates the cystein switch domain of pro-matrilysin (MMP-7): a mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase
J Biol Chem
(2001) - et al.
Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype
Mol Med Today
(1999) Classics in arteriosclerosis research: on experimental cholesterin steatosis and its significance in the origin of some pathological processes by N. Anitschkow and S. Chalatow, translated by Mary Z. Pelias, 1913
Arteriosclerosis
(1938)- et al.
Mechanisms of disease: atherosclerosis, an inflammatory disease (review article)
N Engl J Med
(1999)- et al.
Endothelial dysfunction
Circulation
(2003)
Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis
Nature
The human toll signaling pathway: divergence of nuclear factor κB and JNK/SAPK activation upstream of tumor necrosis factor receptor–associated factor 6 (TRAF6)
J Exp Med
Innate and adaptive immunity in the pathogenesis of atherosclerosis
Circ Res
Osteopontin: between a rock and a hard place
Circ Res
Matrix metalloproteinases in vascular remodelling and atherogenesis: the good, the bad and the ugly
Circ Res
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
Circulation
Mechanisms of progression in native coronary artery disease: role of healed plaque disruption
Heart
Leukocyte recruitment in rupture prone regions of lipid rich plaques: a prominent role for neovascularization?
Cardiovasc Res
Inflammation in atherosclerosis
Nature
Fibrous cap formation or destruction—the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation
Cardiovasc Res
Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture
Circulation
Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells
J Exp Med
Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture
Cardiovasc Res
Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells
Arterioscler Thromb Vasc Biol
Changing concepts of atherogenesis
J Intern Med
CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation
Circ Res
Thrombin potently stimulates cytokine production in human vascular smooth muscle cells but not in mononuclear phagocytes
Circ Res
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Dr Alice Tiong is supported by the Australian Postgraduate Award and the Cardiovascular Lipid Research Grant from Pfizer.