Versican: A Promising Therapeutic Target for Post-Myocardial Injury Cardiac Repair.

This review re-evaluates the literature from a matrix-centered perspective and determines how strongly it supports versican as a regulator of myocardial renewal rather than merely a marker of tissue remodeling. The evidence is organized around molecular identity, developmental location, temporal behavior after infarction, and causal intervention. During cardiac formation, versican-rich extracellular matrices recur in cushions, valves, septal and outflow structures, where matrix hydration, cell adhesion, and proteolytic processing accompany morphogenesis. In adult injury models, versican abundance and processing change as fibroblasts, inflammatory cells, and cardiomyocytes pass through different phases of repair and provisional-matrix resolution. Experimental augmentation has been associated with more cardiomyocytes displaying cell-cycle activity, less fibrotic distortion, and better ventricular performance. Candidate mechanisms include integrin-dependent ERK1/2 and Akt signaling, retention of soluble mediators, and modification of local matrix mechanics. Versican is better interpreted as a context-dependent matrix regulator than as a stand-alone cardiomyocyte mitogen. The current data justify further preclinical work, but not direct clinical use. Translation requires identification of the active isoform or fragment, the responsible source, modifying, and target cell populations, the effective time window and clearance mechanisms, proof that cycling cardiomyocytes complete division and integrate electrically, and systematic testing for fibrosis, inflammation, vascular remodeling, and off-target proliferation.