Therapeutic strategies for endothelial dysfunction

INTRODUCTION: A functionally compromised vascular endothelium is associated with tissue-damaging responses including inflammation, immune stimulation, oxidative stress and platelet activation/aggregation and can lead to severe end-organ damage, as implicated in the pathology of several cardiac, cerebral and renal disorders. Multiple noninvasive techniques are available for assessing endothelial dysfunction in clinical settings. Diverse interventions have been identified as having therapeutic potential for treating endothelial dysfunction and preventing its pathophysiological sequellae. AREAS COVERED: Evaluation techniques and interventional treatment approaches for endothelial dysfunction, with particular reference to prevalent cardiovascular and metabolic disorders such as coronary artery disease and diabetes. Limitations of the current treatments and avenues for improved endothelium-targeted therapies. EXPERT OPINION: Beneficial pleiotropic effects of various agents (cardiovascular medicines, antioxidants, nutritional supplements) on vascular endothelial function in humans notwithstanding, a growing body of preclinical data suggests that protein-, cell- and gene-based approaches hold promise for selective therapeutic targeting of the dysfunctional vascular endothelium. Additional efficacy data in appropriate animal models of vascular injury and cardiometabolic disease, further refinement of delivery modalities and continued investigation of the mechanisms underlying endothelial repair and regeneration should help identify the most promising therapeutic approaches for improving endothelial function that merit evaluation in human trials.