Pharmacological Interventions to Prevent Vascular Endothelial Dysfunction: Future Directions

Abstract

Endothelium forms an innermost lining of blood vessel and it regulates the vascular tone and permeability. A healthy vascular endothelium is antiatherogenic in nature because of its properties such as inhibition of platelet aggregation, adhesion cascades, smooth muscle cell proliferation and leukocyte adhesion. Vascular endothelial dysfunction (VED) is associated with reduced synthesis and release of nitric oxide, proinflammatory and prothrombotic properties followed by diminished vasodilation. VED has been implicated in the pathogenesis of artherosclerosis, hypertension, myocardial infarction, heart failure, renal failure and stroke. Various pharmacological interventions such as angiotensin converting enzyme (ACE) inhibitors, statins, insulin sensitizers, L-arginine as well as agents that target endothelial nitric oxide synthase (eNOS) "coupling" such as folates or tetrahydrobiopterin (BH4) have been noted to improve the function of vascular endothelium. In this review, we discussed various recently developed pharmacological interventions to improve the function of endothelium. Moreover, the novel targets sites involved in the pathogenesis of vascular endothelial dysfunction have been delineated.

Aortic Remodelling in Chronic Nicotine-Administered Rat

“…An increased production and/or impaired scavenging action of ROS, i.e., oxidative stress, would perturb local production of NO [ 38 ]. Nitric oxide has been well-established as the most important endothelium-derived vasodilating substances which inhibit smooth muscle proliferation and migration [ 39 ]. The loss of endothelium integrity may promote hypertrophy of aortic media wall which composed mainly of smooth muscle cell.…”

The Vascular Endothelium and Human Diseases

“…Various pharmacological interventions such as angiotensin-converting enzyme (ACE) inhibitors, statins, insulin sensitizers, and L-arginine, as well as agents that target endothelial nitric oxide synthase (eNOS) “coupling” such as folates or tetrahydrobiopterin (BH4) have been noted to improve the function of the endothelium. Various experimental studies have demonstrated the protective action of inhibitors of Rho-kinase, PARP, PTPase, geranyl transferase, and transketolase and of activators of Akt and PKA toward the endothelium, which would be novel future candidates for treating cardiovascular disorders 121 . It is foreseeable that expanding our understanding of endothelial function further will lead to targeted therapies for a myriad of diseases, including cancer, cardiovascular disease, and inflammation.…”

Arsenic Exposure and Cardiovascular Disorders: An Overview

“…Vascular endothelium has anticoagulant and antithrombotic properties and thus maintains the free flow of blood in vessels [11]. Vascular endothelium has been well known to regulate the release of various mediators like nitric oxide (NO), prostanoids, endothelin-1 (ET-1), angiotensin-II (Ang-II), tissue plasminogen activator (tPA), von Willebrand factor (vWF), adhesion molecules and cytokines [12][13][14][15][16].…”