Therapeutic interventions in endothelial dysfunction: endothelium as a target organ

Endothelial dysfunction is recognized as the initial step in the atherosclerotic process. To date, most interventions attempting to improve endothelial dysfunction have targeted one or more of the numerous risk factors that can cause endothelial damage: hypertension (angiotensin-converting enzyme inhibitors and calcium antagonists), hypercholesterolemia (lipid-lowering agents), cigarette smoking (cessation), sedentary lifestyle (increased physical activity), menopause (estrogen replacement therapy), and diabetes mellitus (control of associated metabolic abnormalities). Interventions targeted specifically to the endothelium remain speculative, as the precise mechanisms of endothelial dysfunction are still being elucidated. Several pharmacologic agents have been suggested to achieve vascular protection through mechanisms that go beyond their primary therapeutic (e.g., hypotensive or hypocholesterolemic) actions; examples of these are angiotensin-converting enzyme inhibitors or HMG-CoA reductase inhibitors. Beneficial changes to the endothelium might result from promotion of vasorelaxation, inhibition of vasoconstriction, reduction in the production of free radicals, or other mechanisms that protect the endothelium from injury.