Abraham Seena S, Osorio Juan C, Homma Shunichi, Wang Jie, Thaker Harshwardhan M, Liao James K, Mital Seema
Department of Pediatrics, Columbia University, New York, New York, USA.
J Cardiovasc Pharmacol. 2004 Mar;43(3):454-61. doi: 10.1097/00005344-200403000-00018.
Endothelial dysfunction characterizes heart failure (HF). Simvastatin (Sim) increases endothelial nitric oxide (NO) independent of lipid-lowering. We evaluated the effect of Sim on cardiac function, apoptosis, and NO availability in HF. Five-month-old cardiomyopathic (CM) hamsters were divided into 2 groups: Sim (20 mg/kg, 6 weeks, n = 6) and Untreated (n = 6). Age-matched normal hamsters served as controls (n = 6). Serial echocardiograms were performed to measure LV function. Myocardial apoptosis, eNOS, and capillary density were measured at 6 weeks. Cardiomyopathic hamsters had lower LV shortening fraction (SF) compared with controls (17 +/- 3% vs 59 +/- 2%), higher LV end-diastolic volume (30 +/- 3 vs 6 +/- 2 mL/m2), and lower LV mass/volume ratio (0.5 +/- 0.04 vs 0.72 +/- 0.02 mg/ml, P < 0.001). During follow-up, SF decreased (9 +/- 2%) and LV volume increased (38 +/- 1 mL/m2) in untreated hamsters (P < 0.05 from baseline) but did not change significantly in the Sim group (P < 0.05 vs untreated). Myocardial caspase-3 activity was higher and apoptotic nuclear density was lower in Sim compared with untreated CM hamsters (0.072 +/- 0.02% vs 0.107 +/- 0.03%, P < 0.01). Myocardial capillary density was highest in the Sim group (P < 0.05). eNOS expression was not different between groups. Sim retards the progression of HF in CM hamsters. This may be related to an increase in coronary microvasculature, increase in NO availability, and decreased apoptosis.
内皮功能障碍是心力衰竭（HF）的特征。辛伐他汀（Sim）可独立于降脂作用增加内皮一氧化氮（NO）。我们评估了Sim对HF心脏功能、细胞凋亡和NO可用性的影响。将5月龄的心肌病（CM）仓鼠分为2组：Sim组（20mg/kg，6周，n = 6）和未治疗组（n = 6）。年龄匹配的正常仓鼠作为对照（n = 6）。进行系列超声心动图检查以测量左心室功能。在6周时测量心肌细胞凋亡、内皮型一氧化氮合酶（eNOS）和毛细血管密度。与对照组相比，心肌病仓鼠的左心室缩短分数（SF）较低（17±3%对59±2%），左心室舒张末期容积较高（30±3对6±2 mL/m2），左心室质量/容积比更低（0.5±0.04对0.72±0.02 mg/ml，P<0.001）。在随访期间，未治疗的仓鼠SF降低（9±2%）且左心室容积增加（38±1 mL/m2）（与基线相比P<0.05），但Sim组无明显变化（与未治疗组相比P<0.05）。与未治疗的CM仓鼠相比，Sim组心肌半胱天冬酶-3活性更高，凋亡核密度更低（0.072±0.02%对0.107±0.03%，P<0.01）。Sim组心肌毛细血管密度最高（P<0.05）。各组间eNOS表达无差异。Sim可延缓CM仓鼠HF的进展。这可能与冠状动脉微血管增加、NO可用性增加和细胞凋亡减少有关。
