[Pathophysiological bases of unstable coronary syndrome].
BACKGROUND
The acute coronary syndrome is the manifestation of a plaque rupture in a coronary artery, which can lead to intermittent or prolonged regional myocardial ischemia. In such a situation, the underlying atherosclerotic lesion is a complex one. Moreover, the mechanisms leading to the instability of an atherosclerotic plaque are complex themselves. This makes it problematic to systematically analyze the nature of the acute coronary syndrome. Moreover, no animal model is available to study this process.
Substantial insights into the basis of the acute coronary syndrome have been gathered by pathomorphological analyses, which have helped to identify a number of criteria describing a vulnerable plaque. Clinical studies have helped to identify the thrombotic component as an important aspect of the clinical manifestation of the acute coronary syndrome. Based on such data, well-defined antithrombotic strategies play an important role in today's therapy of the acute coronary syndrome.
Concerning the triggering mechanisms for an acute coronary syndrome, there is a number of suspected processes, the most important of which is local inflammation of the coronary plaque. Inflammatory processes have recently been recognized as important stimulators of vascular modeling during atherogenesis. These inflammatory mechanisms involve a number of different cytokines, cells of the immune system and other components of the immune systems such as the complement cascade. C-reactive protein may even be a link between systemic and local inflammatory processes, because it has been shown to be systemically elevated in patients with unstable angina, and--most recently--has been shown to be involved in the initiation and progression of early atherosclerotic lesions. Local inflammation of the atherosclerotic plaques induces the expression of a number of growth factors and other potent molecules that contribute to vascular remodeling. These substances are acting on smooth muscle cells, fibroblasts as well as on the extracellular matrix and include growth factors, matrixmetalloproteinases and tissue inhibitors of metalloproteinase. Another component of potential significance within the unstable plaque is the process called plaque-angiogenesis. Plaque-angiogenesis occurs within complicated atherosclerotic plaques, the process of angiogenesis leads to destabilization of the extracellular matrix and, moreover, newly formed capillaries are more likely to rupture and may therefore be an important trigger of plaque rupture and of the acute coronary syndrome.
A number of molecular strategies including inhibition of matrix metalloproteinasis or inhibitors of angiogenesis may turn out to stabilize the vulnerable plaque. Until these therapeutic concepts may be used in the clinic, our therapeutic repertoire will mostly consist of antithrombotic and entire antiinflammatory approaches.
Waltenberger
J
J
Abteilung Innere Medizin II (Kardiologie, Angiologie, Pulmonologie, Nephrologie), Universitätsklinikum Ulm. johannes.waltenberger@medizin.uni-ulm.de
D000208:Acute Disease; D000789:Angina, Unstable / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000473:pathology; D005109:Extracellular Matrix / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007249:Inflammation; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D009389:Neovascularization, Pathologic; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013577:Syndrome; D009626:Terminology as Topic
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D006133:Growth Substances; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases