Neovascularization in the human heart is associated with expression of VEGF-A and its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2). Results from cardiomyopexy in ischemic cardiomyopathy.
Cardiomyopexy is a novel means of revascularization in end-stage ischemic heart disease leading to neovascularization and increased perfusion of the damaged heart. So far, the mediators of this process have not yet been identified. However, among others, vascular endothelial growth factor-A (VEGF-A) is a strong candidate for inducing this process. We have performed cardiomyopexy in humans by transplanting a flap of the musculus latissimus dorsi onto the epicardium. One of the patients died 7 weeks after cardiomyopexy due to a septic process unrelated to the underlying cardiac disease. Tissue specimen from the transplanted muscle flap, from the myocardium and from the native musculus latissimus dorsi were analysed by histological and immunohistochemical methods. The transplanted muscle appeared severely degenerated and showed no immunoreactivity for von Willebrandt factor (vWF) and for VEGF-A nor for its receptors KDR and Flt-1. However, a granulation zone had developed next to the transplanted muscle enriched with monocytes and macrophages which is characterized by a network of capillaries reaching into the ischemic myocardium and providing evidence for strong induction of angiogenesis. This process is accompanied by the abundance of VEGF-A expression in the endothelial layer of vessels. In parallel, VEGF-receptor KDR is present in capillaries passing into the subepicardial region supporting the idea of VEGF-A-induced angiogenesis. The spatial expression pattern of VEGF-A and KDR suggests VEGF-A to be a promotor of angiogenesis leading to indirect myocardial revascularization.