Membrane-Associated Matrix Proteolysis and Heart Failure

Abstract

The extracellular matrix (ECM) is a complex entity containing a large portfolio of structural proteins, signaling molecules, and proteases. Changes in the overall integrity and activational state of these ECM constituents can contribute to tissue structure and function, which is certainly true of the myocardium. Changes in the expression patterns and activational states of a family of ECM proteolytic enzymes, the matrix metalloproteinases (MMPs), have been identified in all forms of LV remodeling and can be a contributory factor for the progression to heart failure. However, new clinical and basic research has identified some surprising and unpredicted changes in MMP profiles in LV remodeling processes, such as with pressure or volume overload, as well as with myocardial infarction. From these studies, it has become recognized that proteolytic processing of signaling molecules by certain MMP types, particularly the transmembrane MMPs, may actually facilitate ECM accumulation as well as modulate fibroblast transdifferentiation – both critical events in adverse LV remodeling. Based upon the ever increasing substrates and diversity of biological actions of MMPs, it is likely that continued research regarding the relationship of LV remodeling to this family of proteases will yield new insights into the ECM remodeling process itself as well as new therapeutic targets.

Metabolic Characterization of Myocardial Infarction Using GC-MS-Based Tissue Metabolomics

“…19) In the infarcted myocardia, due to injury to the cardiomyocyte membrane, more glutamic oxaloacetic transaminase (GOT) will be released into the serum, prohibiting the transamination from glutamate to α-ketoglutaric acid in myocardia and leading to the increase of glutamate in infarcted myocardia. In addition, necrotic cardiomyocyte means more proteins are decomposed, 20) which may also contribute to the increased level of glutamate in the infarcted myocardia. Previous studies showed that a higher level of glutamate was correlated with ongoing myocardial ischemia and that it could activate the generation of NO, inducing the production of free radicals and leading to cardiomyocyte death by mediating inflammatory and cytotoxic actions.…”

Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: Relationship to cardiac functions

“…Many types of matrix metalloproteinases are regarded as particularly being related with myocardial remodeling (8,16). For that reason, matrix metalloproteinase inhibitors have been suggested as a potential therapeutic approach in the prevention of cardiovascular diseases.…”

“…In the pathological conditions with unbalanced matrix metalloproteinases activities, changes in tissue inhibitors of matrix metalloproteinases levels are considered important. The pathological effects of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in cardiovascular disease processes that involve vascular remodeling, atherosclerotic plaque instability, and left ventricular remodeling after myocardial infarction are of considerable interest (6)(7)(8).…”

Transcriptional changes in bone marrow stromal cells of patients with heart failure

“…This finding is noteworthy, since the changes in ECM structure and function directly contribute to the adverse myocardial remodeling in HF of various etiology. 6 …”