The Inflammation Paradigm and Coronary Artery Disease: What Celsus, Virchow and Gene Knock Outs Have Taught Us

Guha      Krishnaswamy

Abstract

Atherosclerotic vascular disease is a major cause of morbidity and mortality throughout the world. The clinical manifestations include coronary artery disease and myocardial infarction, cerebrovascular disease, renovascular disease and peripheral vascular disease. Initially considered a bland occlusive disease mediated to a great extent by lipids, atherosclerosis can now be considered an inflammatory disease, in its own right. This has led to a paradigm shift in disease management. We have come a long way since the time of Celsus, Galen, Virchow, Rokitansky and others when the components of the inflammatory cascade were first described. The development of mouse knock out models, improved molecular approaches to studying atheromatous blood vessels and development of sophisticated imaging and biomarker studies have enhanced our understanding of the molecular pathways in atherosclerosis. This brief review will attempt to weave together the historical, biochemical, immunological and molecular developments that have led to our current understanding of a deadly but treatable and potentially preventable disease.

Keywords: Arteriosclerosis, cytokines, inflammation, mast cells, T cells, transcription factors, myocardial infarction, cerebrovascular disease, renovascular disease, hypertension, hyperhomocysteinemia, cell adhesion molecules (CAMs), nitric oxide (NO), histamine, leukotrienes, edema, vasodilatation, angiogenesis, atherogenesis, phagocytosis, innate immune system, endothelium, fibroblasts, homocysteine, pathogen recognition receptors (PRR), Toll-like receptors (TLRs), proteoglycans, lipoproteins, nicotine, vasculopathy, interferon gamma (IFN), tumor necrosis, fibroblast growth factor (FGF), kappaB, atherothrombosis, arrhythmia, cytokine-cytokine-receptor, lipoprotein-lipoprotein receptors, chronic obstructive pulmonary disease (COPD), gingivitis, chlamydiae, mutagenic, multifactorial disease, serum amyloid, myofibroblasts, thrombolysis, angioplasty