Protective effects of coenzyme Q10 against angiotensin II-induced oxidative stress in human umbilical vein endothelial cells.
Angiotensin II is the major effector in the renin-angiotensin system, and angiotensin II-induced oxidative stress and endothelial dysfunction are profoundly implicated in the pathogenesis of hypertension and cardiovascular disease. In the present study, we investigated the effect of an antioxidant reagent, coenzyme Q10, on angiotensin II-induced oxidative stress in human umbilical vein endothelial cells (HUVEC) to assess its potential usefulness for antioxidant therapy. Treatment of HUVEC with coenzyme Q10 (1-10μM) increased its intracellular levels in a concentration-dependent manner. Coenzyme Q10 (10μM) prevented the actions of angiotensin II (100nM): overproduction of reactive oxygen species, increases in expression of p22(phox) and Nox2 subunits of NADPH oxidase, and inhibition of insulin-induced nitric oxide production. In addition, coenzyme Q10 prevented angiotensin II-induced upregulation of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in HUVEC, and inhibited their adhesion to U937 monocytic cells. Moreover, treatment of HUVEC with coenzyme Q10 effectively ameliorated angiotensin II-induced increases in expression of Nox2 subunit of NADPH oxidase, ICAM-1, and VCAM-1. These results provide the first in vitro evidence that coenzyme Q10 is an efficient antioxidant reagent to improve angiotensin II-induced oxidative stress and endothelial dysfunction, possibly relevant to the causes of cardiovascular disease.
Department of Clinical Pharmacology, University of Toyama, Toyama, Japan. htsuneki@pha.u-toyama.ac.jp
Hiroshi
H
Tsuneki
Emi
E
Tokai
Takashi
T
Suzuki
Takayuki
T
Seki
Kyosuke
K
Okubo
Tsutomu
T
Wada
Tadashi
T
Okamoto
Sakuji
S
Koya
Ikuko
I
Kimura
Toshiyasu
T
Sasaoka
D000804:Angiotensin II / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D007328:Insulin; D000804:Angiotensin II; D014451:Ubiquinone; D009569:Nitric Oxide; C024989:coenzyme Q10