Gene Deletion Reveals Unexpected Consequences

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.2,3