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Dr. Stefan Agewall,
Bases (MMPs) are a group of endopeptidases with capacity to cleave components of extracellular matrix, such as collagen and elastin. The ability to modify the tissues is important for several aspects of normal and abnormal physiology. Approximately 20 different MMPs are identified, and they can be subdivided into different groups, according to which components of the extracellular matrix they degrade.
State of the Art - Basic Science
Myocardial infarction is often caused by a plaque rupture. Depletion of matrix components from the fibrous cap caused by an imbalance between synthesis and breakdown leads to cap thinning. This predisposes the fibrous cap to rupture, either spontaneously or in response to haemodynamic or other triggers. Enhanced matrix breakdown has been attributed primarily to MMPs that are expressed in atherosclerotic plaques by inflammatory cells. Dr Newby from Bristol demonstrated a dual role of MMPs. MMPs in macrophages promote rupture whereas MMPs in smooth muscle cells favour stability. Some MMPs may be more harmful than others and the outcome may depend on site and stage of disease.
Myocardial remodeling occurs when the heart is exposed for loading. The load may consist of elevated pressure or a volume load. Dr Pauschinger from Berlin discussed the association between matrix MMPs and myocardial remodeling. He showed data from several studies demonstrating a clear link between matrix MMPs and left ventricular dilatation and that MMP is elevated in patients with heart failure. Dr Pauschinger also discussed the relevance of inflammation in myocardial remodelling and referred to studies showing a correlation between myocardial uPA mRNA expression respectively collagen III and CD3 T-Lymphocytes.
Dr Pasterkamp from Utrecht discussed carotid atherosclerosis as a model for general and coronary atherosclerosis, since ultrasound intima-media thickness measurements of the carotid artery is easy to measure and carotid artery plaques can be harvested following surgical interventions. There are data indicating that MMP activity reflects plaque complexity and plaque morphology/activity. Dr Ferdinandy from Szeged presented possible cellular targets of MMP 2 in cardiac pathology and demonstrated data showing that pharmacological inhibition of MMP-2 signalling protects the heart against ischemia/reperfusion injury.
MMPs are a complex group of endopeptidases with important roles in cardiovascular physiology and pathology. There are at least two possible future clinical applications of this research area. First, there might be a possibility to develop non-invasive tests for detection of plaque vulnerability. At present, we are far away from the desired prognostic marker of ongoing processes contributing to ultimate plaque rupture. Secondarily, MMP function can be modulated to certain pharmacological drugs, and as MMP activity likely contributes to the development of acute coronary syndromes by making the plaques more vulnerable, MMPs may be an important therapeutic target for future drug development. This vision also appears to be far away in the future.
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Matrix metalloproteinases in cardiovascular pathology Symposium - State of the Art in Basic Science
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