Zhou Wei, Chai Hong, Courson Andy, Lin Peter H, Lumsden Alan B, Yao Qizhi, Chen Changyi
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.
J Vasc Surg. 2006 Oct;44(4):853-62. doi: 10.1016/j.jvs.2006.06.012.
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.
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.
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.
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.
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.
同型半胱氨酸是动脉粥样硬化的独立危险因素。本研究的目的是调查银杏叶的主要成分银杏内酯A（GA）是否能阻止同型半胱氨酸诱导的猪冠状动脉内皮功能障碍。
将猪冠状动脉环分为六个治疗组：对照组；同型半胱氨酸（50微摩尔/升）；低剂量（50微摩尔/升）或高剂量（100微摩尔/升）GA；同型半胱氨酸加低剂量或高剂量GA。孵育24小时后，分析这些环对血栓素A2类似物（U46619）、缓激肽和硝普钠的血管舒缩功能。通过实时聚合酶链反应和免疫组织化学分析研究内皮型一氧化氮合酶（eNOS）。通过化学发光分析评估超氧阴离子的产生。
与对照组相比，用同型半胱氨酸处理的环段中内皮依赖性舒张（缓激肽）明显降低（P <.05）。当同型半胱氨酸与低剂量或高剂量GA联合使用时，内皮依赖性舒张明显恢复。所有组之间的最大收缩（U46619）或非内皮依赖性舒张（硝普钠）没有显著差异。此外，同型半胱氨酸处理组中超氧阴离子的产生增加了113%，而对照组与GA/同型半胱氨酸组之间没有统计学上的显著差异。此外，同型半胱氨酸处理组中eNOS信使核糖核酸和蛋白质水平显著降低（P <.05），但在GA/同型半胱氨酸联合组中没有降低。
同型半胱氨酸通过氧化应激和猪冠状动脉中eNOS的下调显著损害内皮依赖性血管舒张。GA有效预防同型半胱氨酸诱导的猪冠状动脉内皮功能障碍和分子变化。本研究强调了GA在控制同型半胱氨酸相关血管损伤和心血管疾病方面的潜在临床益处和应用。
同型半胱氨酸是动脉粥样硬化的独立危险因素。本研究表明，银杏叶的主要成分银杏内酯A有效预防同型半胱氨酸诱导的猪冠状动脉内皮功能障碍和分子变化。本研究强调了银杏内酯A在控制同型半胱氨酸相关血管损伤和心血管疾病方面的潜在临床益处和应用。
