Extracellular Matrix Proteomics in Cardiac Ischemia/Reperfusion

Abstract

Prolonged myocardial ischemia leads to myocyte necrosis, which initiates a localized inflammatory response that catabolizes the cellular debris and initiates deposition of extracellular matrix (ECM) proteins.1 In addition to providing a vital structural framework for the three-dimensional organization of cells, the ECM determines the physical properties of biological tissues and acts as a dynamic microenvironment for cellular signaling. A number of cardiac diseases, including myocardial ischemia and reperfusion (I/R), are associated with qualitative and quantitative alterations in ECM proteins.2 Understanding ECM changes is important for identifying factors that tip the balance between favorable reparative remodeling following myonecrosis and adverse remodeling that leads to progressive ventricular dilatation and congestive heart failure. Article see p 789 ECM proteomics is the comprehensive description of the ECM expressed in a tissue at the time of evaluation. This approach generates a global, integrated view of extracellular processes and networks at the protein level. The goal of ECM proteomics is to reconcile gene activation to a particular extracellular phenotype. The ability to examine multiple proteins simultaneously is a substantial improvement over previous ECM studies that simply evaluated the total concentration of single proteins (ie, collagen) without consideration of type (eg, type I versus III versus IV) or quality (full-length versus partially degraded collagen). In this issue of Circulation , Barallobre-Barreiro and colleagues present an innovative extracellular matridomic approach for the analysis of ECM protein changes in a porcine I/R model.3 With the use of a novel proteomic method to enrich for ECM proteins, tissue from infarcted and border zone regions of the left ventricle (LV) were analyzed separately by liquid chromatography tandem mass spectrometry for peptide identification and compared with control animals without I/R. Using these techniques, they identified 139 ECM proteins in porcine hearts subjected to 2 hours of ischemia followed by …