Tipping the extracellular matrix balance during heart failure progression: do we always go right?

摘要

Matrix metalloproteinases (MMPs) are highly implicated regulators of cardiac remodeling, and multiple teams have measured MMP and tissue inhibitor of metal-loproteinase (TIMP) levels in various cardiac disease models. Animal and human studies have demonstrated that MMPs increase and are positively associated with remodeling parameters [1-3]. Mice with targeted deletion of specific MMPs or the TIMPs have also incriminated particular MMPs and TIMPs, including MMP-2 and 9 and TIMP-1, in adverse remodeling following myocar-dial infarction [4-7]. However, MMP inhibition strategies have not proven effective in limiting post-myocardi-al infarction remodeling [8]. At this juncture, a crucial question to ask is: if MMPs and extracellular matrix (ECM) degradation are on the right side of the scale and TIMPs and ECM accumulation are on the left side, is interfering with the right side (using MMP inhibitors) the only viable therapeutic strategy to tip the balance?