Edwards Jason M, Neeb Zachary P, Alloosh Mouhamad A, Long Xin, Bratz Ian N, Peller Cassandra R, Byrd James P, Kumar Sanjay, Obukhov Alexander G, Sturek Michael
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN 46202-5120, USA.
Cardiovasc Res. 2010 Feb 1;85(3):631-40. doi: 10.1093/cvr/cvp308. Epub 2009 Sep 10.
Stenting attenuates restenosis, but accelerated coronary artery disease (CAD) adjacent to the stent (peri-stent CAD) remains a concern in metabolic syndrome (MetS). Smooth muscle cell proliferation, a major mechanism of CAD, is mediated partly by myoplasmic Ca2+ dysregulation and store-operated Ca2+ entry (SOCE) via canonical transient receptor potential 1 (TRPC1) channels is proposed to play a key role. Exercise is known to prevent Ca2+ dysregulation in CAD. We tested the hypothesis that MetS increases SOCE and peri-stent CAD and exercise attenuates these events.
Groups (n = 9 pigs each) were (i) healthy lean Ossabaw swine fed standard chow, (ii) excess calorie atherogenic diet fed (MetS), and (iii) aerobically exercise trained starting after 50 weeks of development of MetS (XMetS). Bare metal stents were placed after 54 weeks on diets, and CAD and SOCE were assessed 4 weeks later. Coronary cells were dispersed proximal to the stent (peri-stent) and from non-stent segments, and fura-2 fluorescence was used to assess SOCE, which was verified by Ni2+ blockade and insensitivity to nifedipine. XMetS pigs had increased physical work capacity and decreased LDL/HDL (P < 0.05), but no attenuation of robust insulin resistance, glucose intolerance, hypertriglyceridaemia, or hypertension. CAD was greater in peri-stented vs. non-stented artery segments. MetS had the greatest CAD, SOCE, and TRPC1 and STIM1 mRNA and protein expression, which were all attenuated in XMetS.
This is the first report of the protective effect of exercise on native CAD, peri-stent CAD, SOCE, and molecular expression of TRPC1, STIM1, and Orai1 in MetS.
支架置入可减轻再狭窄，但支架附近的冠状动脉疾病（CAD）加速进展（支架周围CAD）仍是代谢综合征（MetS）中的一个问题。平滑肌细胞增殖是CAD的主要机制，部分由肌浆Ca2+调节异常介导，且通过经典瞬时受体电位1（TRPC1）通道的储存-操作性Ca2+内流（SOCE）被认为起关键作用。已知运动可预防CAD中的Ca2+调节异常。我们检验了以下假设：MetS会增加SOCE和支架周围CAD，而运动可减轻这些情况。
分组（每组n = 9头猪）为：（i）喂食标准饲料的健康瘦型奥萨巴猪，（ii）喂食高热量致动脉粥样化饮食（MetS），以及（iii）在MetS发展50周后开始进行有氧运动训练（XMetS）。在饮食54周后植入裸金属支架，4周后评估CAD和SOCE。在支架近端（支架周围）和非支架节段分散冠状动脉细胞，使用fura-2荧光评估SOCE，通过Ni2+阻断和对硝苯地平不敏感进行验证。XMetS猪的体力工作能力增强，低密度脂蛋白/高密度脂蛋白降低（P < 0.05），但对强烈的胰岛素抵抗、葡萄糖不耐受、高甘油三酯血症或高血压无减轻作用。支架置入段动脉的CAD比非支架段更严重。MetS组的CAD、SOCE以及TRPC1和STIM1的mRNA和蛋白表达最高，而这些在XMetS组均减弱。
这是关于运动对MetS中天然CAD、支架周围CAD、SOCE以及TRPC1、STIM1和Orai1分子表达具有保护作用的首份报告。
