Ginkgolide A attenuates homocysteine-induced endothelial dysfunction in porcine coronary arteries.
BACKGROUND
Homocysteine is an independent risk factor for atherosclerosis. The objective of this study was to investigate whether ginkgolide A (GA), a major constituent of Ginkgo biloba, could block homocysteine-induced endothelial dysfunction in porcine coronary arteries.


METHODS
Porcine coronary artery rings were assigned to six treatment groups: control; homocysteine (50 micromol/L); low-dose (50 micromol/L) or high-dose (100 micromol/L) GA; and homocysteine plus low-dose or high-dose GA. After 24 hours' incubation, the rings were analyzed for vasomotor function in response to a thromboxane A2 analogue (U46619), bradykinin, and sodium nitroprusside. Endothelial nitric oxide synthase (eNOS) was studied by using real-time polymerase chain reaction and immunohistochemistry analysis. Superoxide anion production was assessed by chemoluminescence analysis.


RESULTS
Endothelium-dependent relaxation (bradykinin) was significantly reduced in ring segments treated with homocysteine as compared with the control (P < .05). When homocysteine was combined with either low-dose or high-dose GA, endothelium-dependent relaxation was markedly recovered. There was no significant difference in maximal contraction (U46619) or endothelium-independent relaxation (sodium nitroprusside) among all groups. In addition, superoxide anion production was increased by 113% in the homocysteine-treated group, whereas there was no statistically significant difference between the control and GA/homocysteine groups. Furthermore, eNOS messenger RNA and protein levels were substantially reduced in the homocysteine-treated group (P < .05), but not in the GA/homocysteine combined groups.


CONCLUSIONS
Homocysteine significantly impairs endothelium-dependent vasorelaxation through oxidative stress and downregulation of eNOS in porcine coronary arteries. GA effectively prevents homocysteine-induced endothelial dysfunction and molecular changes in porcine coronary arteries. This study underscores the potential clinical benefits and applications of GA in controlling homocysteine-associated vascular injury and cardiovascular disease.


CONCLUSIONS
Homocysteine is an independent risk factor for atherosclerosis. This study showed that ginkgolide A, a major constituent of Ginkgo biloba, effectively prevents homocysteine-induced endothelial dysfunction and molecular changes in porcine coronary arteries. This study underscores potential clinical benefits and applications of ginkgolide A in controlling homocysteine-associated vascular injury and cardiovascular disease.
Zhou
Wei
W
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Chai
Hong
H
Courson
Andy
A
Lin
Peter H
PH
Lumsden
Alan B
AB
Yao
Qizhi
Q
Chen
Changyi
C
D000818:Animals; D003324:Coronary Artery Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D020441:Ginkgo biloba; D006710:Homocysteine / Q000633:toxicity; D066298:In Vitro Techniques; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013552:Swine; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
D028321:Plant Preparations; D006710:Homocysteine; D012313:RNA; D052250:Nitric Oxide Synthase Type III