The myocardial ECM is a complex entity which forms a reservoir for bioactive signaling molecules (such as angiotensin-II, cytokines, transforming growth factor (TGF), osteopontin (OPN)), matricellular proteins which regulate ECM structure (such as secreted protein acidic and rich in cysteine;SPARC), and proteases and inhibitors (such as the matrix metalloproteinases; MMPs, and secretory-leukocyte-protease-inhibitor; SLPI). Under Normal conditions, dynamic and likely continuous interactions between prototypical receptors such as the angiotensin-II receptor to pro-fibrotic and matricellular proteins, and proteolytic enzymes determine the homeostatic balance of the ECM. The study in this issue of Circulation by Jugdutt and colleagues demonstrated that a shift in the balance if this system occurs within the aging myocardium which would likely favor a more aggressive and amplified remodeling response following an Acute MI.2 Following an acute MI, the release of cytokines such as interleukin-6 (IL-6) occurred which was associated with an induction of TGF, OPN and an array of proteolytic enzymes including MMPs (ie MMP-2, MMP-9) as well as SLPI- many of which are likely released/induced by an acute inflammatory cell response. Jugdutt and colleagues demonstrated that this cytokine/matrikine/proteolytic cascade could be modified with an infusion of an angiotensin-II receptor antagonist.