TY - JOUR
T1 - Primary endothelial dysfunction
T2 - Atherosclerosis
AU - Shimokawa, H.
N1 - Funding Information:
The author wishes to thank Prof Takeshita and coworkers at the Kyushu University School of Medicine and Prof Vanhoutte at the Institute de Re-cherches Internationales Servier for valuable help. The author apologizes for not having cited many other important contributions in this research field due to the limited space available for this article. The original studies by the author presented in this article were supported in part by grants from the National Institute of Health, the American Heart Association, Minnesota Affiliate, and the Japanese Ministry of Education, Science, Sports and Culture.
PY - 1999
Y1 - 1999
N2 - The endothelium synthesizes and releases several vasodilating factors, including nitric oxide, 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 nitric oxide, including receptor-coupled G proteins, the availability of L-arginine, cofactors for endothelial nitric oxide synthase 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 nitric oxide by the endothelium is caused by abnormalities in endothelial signal transduction, availability of L-arginine, cofactors for endothelial nitric oxide synthase and expression of the enzyme. Other mechanisms may also be involved in the impaired endothelium-dependent relaxations in atherosclerosis, including increased destruction of nitric oxide 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.
AB - The endothelium synthesizes and releases several vasodilating factors, including nitric oxide, 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 nitric oxide, including receptor-coupled G proteins, the availability of L-arginine, cofactors for endothelial nitric oxide synthase 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 nitric oxide by the endothelium is caused by abnormalities in endothelial signal transduction, availability of L-arginine, cofactors for endothelial nitric oxide synthase and expression of the enzyme. Other mechanisms may also be involved in the impaired endothelium-dependent relaxations in atherosclerosis, including increased destruction of nitric oxide 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.
KW - Aging
KW - Atherosclerosis
KW - Endothelium-dependent relaxation
KW - Endothelium-derived contracting factor
KW - Endothelium-derived hyperpolarizing factor
KW - Endothelium-derived relaxing factor
KW - G protein
KW - Hypercholesterolemia
KW - Menopause
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=0032991894&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032991894&partnerID=8YFLogxK
U2 - 10.1006/jmcc.1998.0841
DO - 10.1006/jmcc.1998.0841
M3 - Article
C2 - 10072713
AN - SCOPUS:0032991894
VL - 31
SP - 23
EP - 37
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 1
ER -