Danshen inhibits oxysterol-induced endothelial cell apoptosis in vivo.
Oxysterols induce apoptosis in vascular endothelial cells in vitro, but it is not clear whether they do so in vivo. We intravenously injected an oxysterol, cholestan-3beta, 5alpha, 6beta-triol, into rats and quantitatively analyzed endothelial cell apoptosis in the aorta. Oxysterol significantly promoted apoptosis in a time- and dose-dependent fashion. The apoptosis had increased 4.5-fold 6 hrs after injection, and returned to the background level at 48 hrs. An extract of the Chinese herb Danshen as well as probucol abolished triol-induced endothelial cell apoptosis in vitro and in vivo. Since apoptotic cells are quickly cleared, oxysterol-induced apoptosis could significantly affect endothelial integrity over a long period of time. Radical scavengers may be useful for the prevention of endothelial damage.
Nakazawa
Toru
T
National Cardiovascular Center Research Institute, Osaka, Japan.
Xui
Ning
N
Hesong
Zeng
Z
Kinoshita
Mikio
M
Chiba
Tsuyoshi
T
Kaneko
Eiji
E
Yui
Katsumasa
K
Shimokado
Kentaro
K
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002777:Cholestanols / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D010618:Phenanthrolines / Q000008:administration & dosage*; D011341:Probucol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D000975:Antioxidants; D002777:Cholestanols; D004365:Drugs, Chinese Herbal; D000960:Hypolipidemic Agents; D010618:Phenanthrolines; C000474:cholestane-3,5,6-triol; C028972:dan-shen root extract; D011341:Probucol