Myocardial extracellular matrix remodeling in ischemic heart failure

Abstract

Left ventricular (LV) remodeling is a process whereby structural alterations attempt to compensate altered hemodynamic load. In the chronic setting this process becomes maladaptive, self-sustaining and is associated with worsened survival. The extracellular matrix (ECM) of the heart, once believed an inert scaffold for cardiomyocytes, is now known to play an important role in LV remodeling. The enzyme system primarily responsible for ECM turnover is the matrix metalloproteinases (MMPs), and these enzymes are robustly altered in cardiovascular pathologies, including myocardial infarction (MI) and ischemic heart failure. A cause-and-effect relationship has been established between MMPs and LV remodeling post MI, as MMP inhibition prevents LV dilation and preserves cardiac function in animal models of infarction. In spite of this, initial clinical experience with MMP inhibition post MI has been disappointing. This review examines the structural and functional roles of the myocardial ECM, the evidence for MMP involvement in LV remodeling, and recent investigations into MMPs as prognostic markers and therapeutic targets.

Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance

“…In the heart, extracellular matrix is not a static skeleton but a dynamic system (102–104). In contrast, it has become clear that altered matrix turnover is an active component of the process of cardiac remodeling (102–104).…”

“…In contrast, it has become clear that altered matrix turnover is an active component of the process of cardiac remodeling (102–104). MMP is a family of enzymes that includes more than 20 members (collagenases, gelatinases and stromelysins) and is the major regulator of extracellular tissue breakdown (102–104).…”

IGF-II/mannose 6-phosphate receptor activation induces metalloproteinase-9 matrix activity and increases plasminogen activator expression in H9c2 cardiomyoblast cells

“…When responding to pathological stresses, e.g., hypertension and myocardial infarction, the heart undergoes a myocardial extracellular matrix (ECM) remodeling that brings about decreased microvasculature and increased ECM deposition, which may in turn contribute to heart failure development (Berk et al 2007, Gallagher et al 2007. The ECM degrading enzymes such as plasminogen activation (PA) system and the matrix metalloproteinase (MMP) system (Cleutjens & Creemers 2002, Spinale 2002) are increased in animals and patients with systolic heart failure (Spinale et al 2000, Gaertner et al 2005.…”

Physical Properties of Poly (N-isopropylacrylamide) Hydrogel Promote its Effects on Cardiac Protection after Myocardial Infarction

“…16 Previous findings demonstrated the effectiveness of biomaterials in cardiac protection, 3,4,7 -10,12 but data on the possible role of biomaterials in MI treatment are still scarce.…”