Restoring the Dysfunctional Endothelium

Abstract

Nowadays the endothelium is considered a key determinant of vascular health. NO is the principal mediator of all endothelial protective effects, due to its antiinflammatory, antiproliferative, immunomodulatory and vasorelaxant properties. On the contrary, a growing body of evidence suggests that endothelial dysfunction is associated with cardiovascular events. Emerging data suggest that acute coronary syndromes (ACS) may involve a complex interplay between endothelial dysfunction, inflammation and thrombosis. Despite the success in reducing the mortality from acute cardiovascular events, the incidence of cardiovascular disease and its complication continues to increase. New insights into mechanisms of endothelial dysfunction, such as a better understanding of the regulation of vascular sources of oxygen radicals, may lead to novel therapeutic strategies with the potential to improve prognosis. The key pharmacological agents that improve clinical outcome in high-risk patients are statins, ACE-inhibitors or angiotensin receptor antagonists. Compelling scientific evidence suggests that these medications are effective in improving endothelial function. The present review focuses on the potential importance of benefits on endothelium of these medicaments in the management of acute coronary syndromes.

c-Jun N-Terminal Kinase 2 Deficiency Protects Against Hypercholesterolemia-Induced Endothelial Dysfunction and Oxidative Stress

“…This balance is impaired in hypercholesterolemia and atherosclerosis. 20,21 Endothelial dysfunction, reflected by impaired endothelium-dependent relaxation, occurs in experimental models of hypercholesterolemia, as was confirmed in WT mice of this study. 22,23 Similarly, many clinical studies reported abnormal endothelium-dependent vasodilation in hypercholesterolemic patients.…”

Association Between Endothelial Dysfunction and Acute Brain Dysfunction During Critical Illness

“…Thus, if future studies confirm that Endo_PAT RHI measurements are associated with patients' acute cognitive outcomes, endothelial function monitoring may serve as a prognostic tool in the ICU as well as a means to study the impact of therapies aimed at reducing brain dysfunction through interventions that enhance endothelial function (e.g., statin pharmacotherapy, early physical rehabilitation). 45 Our results are also in agreement with the growing body of literature examining tissue perfusion abnormalities as measured by near-infrared spectroscopy. Consistently low tissue oxygenation was associated with worse organ failure in small cohorts of critically ill patients, 46 and lower tissue oxygen saturation and slower recovery rate after an ischemic period has been correlated to perfusion abnormaities.…”

Previous Statin Use and High-Resolution Magnetic Resonance Imaging Characteristics of Intracranial Atherosclerotic Plaque

“…Recent studies have revealed a protective effect of statins against vascular disease risk, including a reduction of systemic inflammation and improvement in endothelial dysfunction. [16][17][18] Furthermore, statins have been shown to exert many pleiotropic effects, [19][20][21] which could explain, at least in part, the greater reduction in cardiovascular risk with statin use than other LDL-lowering modalities. 22,23 The ability of statins to stabilize the culprit lesions of atherosclerotic plaque and prevent them from rupturing has also been demonstrated in symptomatic coronary arteries [24][25][26] and extracranial carotid arteries.…”