Reconstituted high-density lipoprotein attenuates postinfarction left ventricular remodeling in rats
Reconstituted high-density lipoprotein attenuates postinfarction left ventricular remodeling in rats
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DOI：
10.1016/j.atherosclerosis.2008.05.056
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发表时间：
2009-03-01
期刊：
影响因子：
5.3
通讯作者：
Saku, Keijiro
中科院分区：
文献类型：
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作者：
Kiya, Yoshihiro;Miura, Shin-ichiro;Saku, Keijiro
由于对重组高密度脂蛋白（rHDL）在左心室（LV）重构中的作用知之甚少，因此在急性心肌梗死（MI）后的大鼠中检测了这些作用。16只雄性Wistar大鼠随机分为三组：假手术组（n =6），心肌梗死组（MI组，n=5）接受左冠状动脉近端周围永久性结扎并静脉注射安慰剂（MI组，n=5）或rHDL（含载脂蛋白-16 mg/kg） （MI + rHDL组，n=5）。rHDL每周输注1次，连续4周。此外，还进行了体外实验，以检验rHDL的作用。心肌梗死+ rHDL组左室射血分数（EF）在第1周至第4周显著升高，左室收缩末期直径减小，而心肌梗死组左室大小和功能渐进式恶化。与MI组相比，MI +rHDL组左室心肌纤维化面积明显减少，而MI +rHDL组左室毛细血管密度和细胞大小均无明显增加。有趣的是，MI + rHDL组显示视网膜母细胞瘤和ERK（细胞外信号调节激酶）的显著激活，但没有裂解caspase-3， p38 MAPK或Jun n末端激酶。rHDL抑制h2o2诱导的肌细胞生长阻滞。这种作用被ERK抑制剂PD98059阻断。综上所述，rhdl促进细胞存活具有有益的形态学作用，有助于防止心肌梗死后左室重构和改善功能，并可能通过肌细胞ERK途径防止细胞生长停滞。2008爱思唯尔爱尔兰有限公司版权所有。
Since little is known about the effects of reconstituted high-density lipoprotein (rHDL) in left ventricular (LV) remodeling, these effects were examined in rats after acute myocardial infraction (MI). Sixteen male Wistar rats were randomly divided into three groups: Sham-operated (n =6), and MI rats that received a permanent ligation around the proximal left coronary artery and infusions of placebo (MI group, n=5) or rHDL (containing as apolipoproteinA-16 mg/kg) administered intravenously (MI + rHDL group, it -5). rHDL was infused once a week for 4 weeks. In addition, in vitro assays were performed to examine the effect of rHDL. The MI + rHDL group showed a significant increase in LV ejection fraction (EF) between weeks I and 4, a decrease in LV end-systolic diameter, compared with the progressive deterioration of LV size and function in the MI group. In addition, the MI + rHDL group showed a significant decrease in fibrotic area of MI in LV compared to that in the MI group, while there were no significant increases in capillary density or cell size in LV in the MI +rHDL group. Interestingly, the MI + rHDL group showed a significant activation of retinoblastoma and ERK (extracellular-signal-regulated kinase) but not cleaved caspase-3, p38 MAPK or Jun N-terminal kinase. rHDL suppressed H2O2-induced arrest of cell growth in myocytes. This effect was blocked by PD98059, an ERK inhibitor. In conclusions, rHDL-promoted cell survival has beneficial morphological effects that help to prevent LV remodeling and improve function after MI, and may prevent arrest of cell growth through ERK pathway in myocytes. (C) 2008 Elsevier Ireland Ltd. All rights reserved.