Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Surgery. 2010 Aug;148(2):453-62. doi: 10.1016/j.surg.2010.04.013. Epub 2010 Jun 8.
Resveratrol has been reported to induce angiogenesis in ischemic tissue. We hypothesized that high-dose resveratrol would improve native angiogenesis in a swine model of metabolic syndrome and chronic myocardial ischemia.
Yorkshire swine were fed a normal diet (Control, n = 7), hypercholesterolemic diet (HCD, n = 7), or hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCD-R; n = 7) beginning 1 month prior to surgery. Chronic ischemia was created by placing an ameroid constrictor on the left circumflex coronary artery. After 7 weeks, swine underwent functional MRI, coronary angiography, and serum and heart tissue harvest for analysis.
HCD-R animals had lower body mass index (P < .001), total cholesterol (P < .001), low-density lipoprotein (LDL; P < .001), blood glucose levels (P < .001), and systolic blood pressure (P = .03) than HCD animals. There was no difference in regional myocardial function at 7 weeks (P = .25). Coronary angiograms revealed no difference in Rentrop collateral scores (P = .68). Staining for platelet endothelial cell adhesion molecule-1 demonstrated higher capillary density in the Control group (versus HCD and HCD-R; P = .02). Immunoblotting demonstrated decreased expression of the pro-angiogenic protein vascular endothelial (VE)-cadherin (P = .002) and an increase in anti-angiogenic proteins angiostatin (P = .001) and thrombospondin (P = .02) in the HCD and HCD-R groups. Matrix metalloprotease 2 (MMP 2; P = .47) and MMP 9 (P = .12) were not different among groups.
Supplemental resveratrol positively modified cardiovascular risk factors including body mass index, cholesterol, glucose tolerance, and systolic blood pressure. However, it did not increase native collateral formation in the ischemic myocardium. This may be a result of increased angiostatin and thrombospondin leading to decreased expression of VE-cadherin and other pro-angiogenic factors.
白藜芦醇已被报道可诱导缺血组织中的血管生成。我们假设高剂量白藜芦醇会改善代谢综合征和慢性心肌缺血猪模型中的内源性血管生成。
约克夏猪在手术前 1 个月开始分别给予正常饮食（对照组，n=7）、高胆固醇饮食（HCD，n=7）或高胆固醇饮食加白藜芦醇补充剂（每天 100mg/kg 口服，HCD-R，n=7）。通过在左回旋冠状动脉上放置一个 ameroid 缩窄器来创建慢性缺血。7 周后，猪接受功能磁共振成像、冠状动脉造影以及血清和心脏组织采集用于分析。
HCD-R 动物的体重指数（P<0.001）、总胆固醇（P<0.001）、低密度脂蛋白（LDL；P<0.001）、血糖水平（P<0.001）和收缩压（P=0.03）均低于 HCD 动物。7 周时区域性心肌功能无差异（P=0.25）。冠状动脉造影显示 Rentrop 侧支评分无差异（P=0.68）。血小板内皮细胞黏附分子-1染色显示对照组的毛细血管密度较高（与 HCD 和 HCD-R 相比；P=0.02）。免疫印迹显示促血管生成蛋白血管内皮（VE）-钙黏蛋白的表达减少（P=0.002），以及 HCD 和 HCD-R 组中抗血管生成蛋白血管生成抑制素（P=0.001）和血栓素（P=0.02）的表达增加。基质金属蛋白酶 2（MMP 2；P=0.47）和 MMP 9（P=0.12）在各组之间无差异。
补充白藜芦醇可积极改变心血管危险因素，包括体重指数、胆固醇、葡萄糖耐量和收缩压。然而，它并没有增加缺血心肌中的内源性侧支形成。这可能是由于血管生成抑制素和血栓素的增加导致 VE-钙黏蛋白和其他促血管生成因子的表达减少。
