Endothelial dysfunction as a novel therapeutic target in atherosclerosis

H. Shimokawa

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

The endothelium synthesizes and releases several vasodilating factors, including nitric oxide (NO), endothelium-derived hyperpolarizing factor and prostacyclin. Under certain conditions, it also liberates vasocontracting factors. Thus, the endothelium plays an important role in regulating vascular homeostasis. Several intracellular mechanisms are involved in the synthesis of NO, including receptor-coupled G-proteins, the availability of L- arginine, co-factors for endothelial nitric oxide synthase (eNOS) and the expression of the enzyme. Endothelial dysfunction by aging, menopause and hypercholesterolemia is involved in the development of atherosclerotic vascular lesions and predisposes the blood vessel to several vascular disorders, such as vasospasm and thrombosis. Multiple mechanisms are apparently involved in the pathogenesis of the endothelial dysfunction in atherosclerosis. The reduced production of NO by the endothelium is caused by abnormalities in endothelial signal transduction, availability of L-arginine or of co-factors for eNOS, and expression of the enzyme. Other mechanisms may also be involved in the impaired endothelium-dependent relaxations in atherosclerosis, including increased destruction of NO by superoxide anion, altered responsiveness of vascular smooth muscle and concomitant release of vasocontracting factors. In addition to the treatment of the underlying risk factors, several pharmacological agents can improve endothelial dysfunction in atherosclerosis. Thus, the endothelium is a novel therapeutic target for the treatment of atherosclerotic cardiovascular disease.

Original languageEnglish
Pages (from-to)271-277
Number of pages7
JournalDrug News and Perspectives
Volume12
Issue number5
DOIs
Publication statusPublished - 1999 Jul 28
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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