Metalloproteinases (
MMPs, also called matrixins) are extracellular
proteolytic enzymes involved in the degradation of both matrix and nonmatrix
proteins. Currently, 25
MMPs have been identified in humans, and the overexpression of one or more
MMPs has been implicated in several pathologies, spanning from
cancer to rheumathoid
arthritis to
cardiovascular disease. While research over the past 20 years has focused on understanding
MMP biology and selectively inhibiting
MMP activity, key issues that remain to be addressed include
MMP roles in the context of normal versus pathological conditions and whether globally inhibiting
MMPs improves or deteriorates overall organ function. In terms of
cardiovascular disease, increased
MMP expression has been demonstrated in the setting of
myocardial ischemia,
reperfusion injury, and during the progression to
congestive heart failure.
MMPs are also major contributors to the progression of atherosclerotic lesions. In this review, we focus on cardiovascular effects produced by
PD 166793, a wide-broad spectrum
MMP inhibitor, originally developed by Parke-Davis (now Pfizer). We will briefly review its structure, mechanism of action, and inhibitory capacity. Finally, we will illustrate the cardiac contexts, both in vivo and in vitro, in which
PD166793 administration has proven beneficial.