Diversity of Myocardial Interstitial Proteolytic Pathways

A fundamental objective of cardiovascular medicine is the early detection of structural changes within the heart and vasculature that would be harbingers of disease. For example, a much greater emphasis has been placed on identifying patients with underlying changes in left ventricular (LV) myocardial structure before the onset of occult LV dysfunction and symptomatic heart failure.1 These changes in LV myocardial form and function have been generically termed LV remodeling, and an important research direction is to identify critical pathways that contribute to this adverse remodeling process. Although significant past research efforts have been made to identify changes in cardiocyte structure and function, LV remodeling is a multifactorial process involving both cellular and extracellular pathways. An evolving concept is that a significant interplay exists among biological signaling molecules, transmembrane proteins, and proteases within the myocardial interstitial space, which in turn promulgates LV remodeling. In the present issue of Circulation , a pair of studies is presented that further demonstrate the diverse functionality of proteases that exist within the myocardial interstitial space and how genetically altering these proteolytic pathways can result in unexpected consequences for LV remodeling process.2,3Articles see p 2082 and p 2094The matrix metalloproteinases (MMPs) were once considered a small set of proteases with a rather limited role in terms of degrading structural proteins within the interstitium. However, as the number of MMPs and the portfolio of proteolytic substrates continue to grow, so does the recognized functionality of these proteases in the myocardial remodeling process. The generalized nomenclature for the MMPs was initially established on what was considered to be the fundamental proteolytic targets for each MMP class; hence the use of collagenases for the MMP types MMP-1, -8 and -13 and the gelatinases (processing of denatured collagen) for MMP-2 and MMP-9. However, …