Cardiovascular Risk and Matrix Metalloproteinase Polymorphisms: Not Just a Simple Substitution.

Abstract

Cardiovascular remodeling is a process by which structural changes occur within the vascular compartment and the myocardium and are hallmark events in the development and progression of cardiovascular disease. This remodeling process is multifactorial entailing biological shifts in molecular, cellular, and extracellular matrix (ECM) structure and function. The ECM, for example, plays a critical role in maintaining normal vascular and myocardial architecture, and proteolytic turnover of the ECM, driven in large part by the induction and activation of matrix metalloproteinases (MMPs), is a major determinant of ECM structure and function. The MMPs are tightly regulated by transcriptional, post-transcriptional, and post-translational checkpoints. Transcriptional regulation of MMPs is primarily determined by upstream gene promoter activity, whereby several intracellular signaling factors bind to specific sequences within the MMP promoter sequence. As such, there has been considerable interest in nucleic acid substitutions (ie, polymorphisms) that occur within the MMP promoter regions and relation to overall MMP levels, and most importantly, relation to cardiovascular outcomes.1,2 See Article by Salminen et al There have been several MMP polymorphisms identified in key MMP types, which include the collagenases (MMP-1, -8), the gelatinases (MMP-2, MMP-9), and stromelysins (MMP-3). A brief synopsis of MMP polymorphisms with respect to cardiovascular remodeling processes and selected citations is provided in Table.2–19 This summary table is by no means exhaustive but underscores the fact that several polymorphisms, primarily within the MMP promoter regions, have been identified and associated with subsets of patients at risk for cardiovascular events. Several of the …