Erythropoietin and ventricular remodelling: a VEGF-dependent neovascularity.

摘要

To uncover novel therapeutics for heart failure (HF), attention has focussed on the biological factors that underlie the transition from an initially adaptive hypertrophic response to a maladaptive state that promotes progressive cardiac dysfunction. The cardiac microvas-culature is an important factor in this regard inasmuch as insufficient capillary growth is thought to be an important contributor to progressive dysfunction and remodelling in HF. Unlike the increased capillary density seen in conditions of physiological cardiac hypertrophy, reduced microvascular density and fewer capillaries are commonly observed in failing hearts. Microvascular rarefaction in pathological hypertrophy imparts many untoward effects, including myocardial ischaemia due to deficient oxygen supply, inefficient cardiac metabolism, myocyte loss, inflammation, fibrosis, and contractile dysfunction. Changes in myocardial capillary density during myocardial hypertrophy have been linked to the expression of angio-genic factors such as vascular endothelial growth factor (VEGF). In murine models, pressure overload induces the expression of VEGF and angiopoietin 2 during the adaptive phase of hypertrophy, whereas blockade of VEGF signalling decreases myocardial neovascu-larization and accelerates the transition to failure.6 Hence, restoration of the cardiac microvasculature theoretically represents a viable strategy to improve cardiac function in HF.