Simvastatin prevents coronary microvascular remodeling in renovascular hypertensive pigs.
Simvastatin prevents coronary microvascular remodeling in renovascular hypertensive pigs.
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DOI：
10.1681/asn.2006090976
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发表时间：
2007-04
期刊：
影响因子：
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通讯作者：
Xiang-yang Zhu;E. Daghini;A. Chade;C. Napoli;E. Ritman;A. Lerman;L. Lerman
中科院分区：
文献类型：
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作者：
Xiang-yang Zhu;E. Daghini;A. Chade;C. Napoli;E. Ritman;A. Lerman;L. Lerman
高血压和慢性肾病患者有患心血管疾病的风险，可能与炎症有关。他汀类药物对血管结构具有有益的抗炎作用，而与胆固醇降低无关。据推测，辛伐他汀治疗可以改善猪肾血管性高血压（RVH）心肌微血管结构的改变。12周后研究了三组猪：正常（n = 7），RVH（n = 7），或RVH+辛伐他汀（RVH + S; 80 mg/d; n = 6）。使用电子束计算机断层扫描在体内测定左心室肌肉质量和心肌灌注，然后使用微型计算机断层扫描离体扫描心肌样品，以测量原位心肌微血管的空间密度（80至500 μ m）。在心肌组织中测定毛细血管密度和炎性和生长因子的心肌表达。辛伐他汀对炎症诱导的管形成的影响在体外在暴露于TNF-α的人脐静脉内皮细胞中进行了评价。RVH和RVH + S具有相似的动脉压和血清肌酐升高。然而，辛伐他汀可预防左心室肥厚，并增加心肌灌注。与正常组相比，RVH组微血管密度增加（169.6 +/-21 vs. 107.7 +/-15.2 vessels/cm 2; P <0.05），RVH + S组微血管密度降低（72.5 +/-14.9 vessels/cm 2），而毛细血管密度与正常组相似。RVH也增加心肌炎症和生长因子的表达，辛伐他汀逆转。此外，辛伐他汀在体外减弱TNF-α诱导的血管生成。辛伐他汀可防止实验性RVH中心肌微血管重塑和肥大，与降脂无关。这种保护作用部分由炎症细胞因子的钝化表达以及血管生成活性介导。
Patients with hypertension and chronic kidney disease are at risk for cardiovascular diseases, possibly related to inflammation. Statins have beneficial anti-inflammatory effects on vascular structure regardless of cholesterol reduction. It was hypothesized that alterations in myocardial microvascular structure in swine renovascular hypertension (RVH) would be improved by simvastatin treatment. Three groups of pigs were studied after 12 wk: normal (n = 7), RVH (n = 7), or RVH+simvastatin (RVH+S; 80 mg/d; n = 6). Left ventricular muscle mass and myocardial perfusion were determined in vivo using electron beam computed tomography, and myocardial samples then were scanned ex vivo using micro-computed tomography for measurement of the spatial density of myocardial microvessels (80 to 500 microm) in situ. Capillary density and myocardial expression of inflammatory and growth factors were determined in myocardial tissue. The effects of simvastatin on inflammation-induced tube formation were evaluated in vitro in human umbilical vein endothelial cells that were exposed to TNF-alpha. RVH and RVH+S had similarly increased arterial pressure and serum creatinine. However, left ventricular hypertrophy was prevented by simvastatin, and myocardial perfusion was increased. Compared with normal, RVH showed increased spatial density of microvessels (169.6 +/- 21 versus 107.7 +/- 15.2 vessels/cm(2); P < 0.05), which was decreased in RVH+S (72.5 +/- 14.9 vessels/cm(2)), whereas capillary density remained similar to normal. RVH also increased myocardial expression of inflammatory and growth factors, which were reversed by simvastatin. Furthermore, simvastatin attenuated TNF-alpha-induced angiogenesis in vitro. Simvastatin prevents myocardial microvascular remodeling and hypertrophy in experimental RVH independent of lipid lowering. This protective effect is partly mediated by blunted expression as well as angiogenic activity of inflammatory cytokines.