The Endothelium as a Target for the Treatment of Heart Failure

The functional integrity of endothelial cells is a marker and a prerequisite for vascular health. It is well established that the endothelium not only modulates, but also mediates vascular disease processes. Certain diseases such as diabetes, dyslipidaemia, obesity, and arterial hypertension advance endothelial injury. The disease process induces cellular and functional changes in endothelial cells leading to a pathophysiological phenomenon referred to as endothelial cell dysfunction, which involves abnormal vasomotion, an imbalance in reactive oxygen species and nitric oxide, the activation of inflammation, and disruption of the coagulation process of the endothelial cells. With this knowledge, it is now known that vascular function plays a central role in the development and progression of heart failure (HF). HF is the primary cause of patient hospitalization. There is a strong desire to intervene and prevent the growing HF epidemic. Over the last decade, numerous therapies have been evaluated but few have led to positive results in the later stages of clinical trials. Efforts are currently being made to understand the pathophysiology of endothelial dysfunction and use this knowledge to identify novel agents or therapeutic targets that will improve the outcome of patients with HF and restore the normal function of the endothelium. The purpose of this review is to present a brief summary of the traditional approaches that have been taken to improve endothelial dysfunction and combat HF and, more importantly, to discuss some novel therapeutic approaches that are still under investigation, including the use of gene therapy and nanocarriers as means of delivering targets to the dysfunctional endothelium as treatment for HF.