Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia.
Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia.
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DOI：
10.1161/circulationaha.109.920132
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发表时间：
2010-09-14
期刊：
影响因子：
37.8
通讯作者：
Sellke FW
中科院分区：
文献类型：
--
作者：
Robich MP;Osipov RM;Nezafat R;Feng J;Clements RT;Bianchi C;Boodhwani M;Coady MA;Laham RJ;Sellke FW
白藜芦醇可以提供对冠状动脉疾病的保护。我们假设补充白藜芦醇将改善高胆固醇血症和慢性心肌缺血猪的缺血区域的心脏灌注。给约克郡猪喂食正常饮食（对照，n=7）、高胆固醇血症饮食（HCC，n=7）或补充白藜芦醇的高胆固醇血症饮食（口服100 mg/kg/天，HCRV，n=7）。4周后，将Ameroid缩窄器放置在左回旋动脉上。7周后，在处死和组织收获之前，动物接受心脏磁共振成像和冠状动脉血管造影。HCRV动物的总胆固醇降低约30%（p<0.001）。局部室壁运动分析表明HCC猪的下外侧功能从基线至7周显著降低（p=0.04）。HCRV猪的局部功能从基线至7周无显著变化（p=0.32）。与HCC猪相比，HCRV猪在应激期间的组织血流量高2.8倍（p=0.04）。在HCC猪中，对P物质的内皮依赖性微血管舒张反应减弱，这是由白藜芦醇治疗挽救的（p=0.004）。毛细血管密度（PECAM-1染色）显示HCC和HCRV猪中的毛细血管均少于对照猪（p=0.02）。免疫印迹分析表明，HCRV与HCC猪相比，以下血管生成标志物的表达显著更高：VEGF（p=0.002）、peNOS（ser 1177）（p=0.04）、NFkB（p=0.004）和pAkt（thr 308）（p=0.001）。补充白藜芦醇可减弱局部室壁运动异常，改善侧支依赖性区域的心肌灌注，保护内皮依赖性冠状血管功能，并上调与VEGF信号通路相关的血管生成标志物。
Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac magnetic resonance imaging and coronary angiography 7 weeks later, prior to sacrifice and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (p<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (p=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (p=0.32). Tissue blood flow during stress was 2.8 fold greater in HCRV swine when compared to HCC swine (p=0.04). Endothelial dependent microvascular relaxation response to Substance P was diminished in HCC swine which was rescued by resveratrol treatment (p=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine v. control swine (p=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV v. HCC swine of the following markers of angiogenesis: VEGF (p=0.002), peNOS(ser1177)(p=0.04), NFkB (p=0.004), and pAkt(thr308)(p=0.001). Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelial dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.