Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature.
Matrix metalloproteinases (MMPs) have been shown to play significant roles in a number of physiological as well as pathological processes. Best known to proteolyse components of the extracellular matrix, MMPs have recently been discovered to also target a growing list of proteins apart from these, both inside and outside the cell. MMPs have also been traditionally thought of as enzymes involved in chronic processes such as angiogenesis, remodelling and atherosclerosis on a days-week time-scale. However they are now understood to also act acutely in response to oxidative stress on a minutes time-scale on non-extracellular matrix substrates. This review focuses on the acute actions and both extracellular and intracellular targets of two prominent MMP family members, MMP-2 and -9, in cardiovascular diseases including ischaemia/reperfusion injury, inflammatory heart disease, septic shock and pre-eclampsia. Also discussed are various ways of regulating MMP activity, including post-translational mechanisms, the endogenous tissue inhibitors of metalloproteinases and pharmacological inhibitors. A comprehensive understanding of MMP biology is necessary for the development of novel pharmacological therapies to combat the impact of cardiovascular disease.
Chow
A K
AK
Department of Pediatrics, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada.
Cena
J
J
Schulz
R
R
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009206:Myocardium / Q000378:metabolism
D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9