Systemic relaxin administration stimulates angiogenic cytokine expression and vessel formation in a rat myocardial infarct model

Abstract

The myocardium consists of three integrated components: myocytes, extracellular matrix, and a capillary microcirculation. Myocardial injury following vessel occlusion results in the formation of an ischemic zone whose size and position in the myocardium is determined by the anatomical region over which the capillary bed, supplied by the occluded vessel, lies [1]. Ischemia results in the onset of myocyte necrosis and generates an inflammatory response driven by infiltrating neutrophils and macrophages [2,3]. Neutrophils initiate local degradation of matrix at infarct sites by secretion of metalloproteases (MMPs) [4,5]. In an attempt to initiate repair, macrophages and dying myocytes then release TGFβ1 and vascular endothelial growth factor (VEGF) [6]. An early increase in levels of TGFβ1 in the infarct zone results in macrophage and fibroblast chemotaxis and fibroblast proliferation [2,7–9]. These ischemic-induced changes in turn increase VEGF and basic fibroblast growth factor (bFGF) levels [10]. Concomitantly, stress-induced changes to endothelium results in the expression of monocyte chemoattractant protein-1 (MCP-1) and endothelial integrins, which facilitate increased macrophage infiltration [2,11]. The early increase in MMPs, and subsequent increases in VEGF and bFGF levels, are essential requirements for the onset of neoangiogenesis of microvascular endothelial cells in the myocardium.