Pravastatin improves remodeling and cardiac function after myocardial infarction by an antiinflammatory mechanism rather than by the induction of angiogenesis
Pravastatin improves remodeling and cardiac function after myocardial infarction by an antiinflammatory mechanism rather than by the induction of angiogenesis
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DOI：
10.1016/j.athoracsur.2005.12.065
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发表时间：
2006-06-01
影响因子：
4.6
通讯作者：
Sellke, Frank W.
中科院分区：
文献类型：
--
作者：
Li, Tao-Sheng;Takahashi, Masaya;Sellke, Frank W.
背景最近的研究报道，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（或他汀类药物）可以改善血管生成。使用急性梗死模型，我们研究了他汀类药物单独或与细胞治疗联合对血管生成的治疗价值。Zucker肥胖大鼠是一种以肥胖、高血糖和高脂血症为特征的品系，用于本研究。结扎左前降支动脉后，大鼠每天口服普伐他汀5或50 mg/kg，或心肌内注射总计2 x 10（7）个自体骨髓单核细胞，或两者联合。在治疗前、治疗后7、14和28天通过超声心动图评估心功能。治疗后28天进行梗死心肌微血管密度、淋巴细胞浸润和胶原纤维积聚的组织学评估。无论是细胞植入还是普伐他汀单独给药，心脏功能均得到改善，胶原沉积显著减少，但两者联合应用未见协同作用。然而，微血管密度在梗死心肌增加，只有骨髓单个核细胞的植入，而不是由普伐他汀管理。普伐他汀导致白细胞介素1 β和肿瘤坏死因子-α的血清水平显着下降，也在CD 45阳性细胞的浸润，但不是CD 117阳性干细胞，在梗死心肌。口服普伐他汀14天后，循环中CD 34阳性细胞数量和内皮细胞分化能力均未显著增加。普伐他汀可以改善心肌梗死后的心功能，但是通过一种抑制机制，而不是通过诱导治疗性血管生成。联合应用普伐他汀和骨髓单个核细胞移植对诱导血管生成无协同作用。
Background. Recent studies have reported that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (or statins) can improve angiogenesis. Using an acute infarction model, we examined the therapeutic merit of statins on angiogenesis, alone and in combination with cell-based therapy.Methods. Zucker fatty rats, a strain characterized by obesity, hyperglycemia, and hyperlipidemia, were used for this study. After ligating the left anterior descending artery, rats were given oral pravastatin 5 or 50 mg/kg per day, or an intramyocardial injection of a total 2 x 10(7) autologous bone marrow mononuclear cells, or a combination of both. Cardiac function was assessed by echo-cardiography before treatment, then 7, 14, and 28 days after treatment. Histologic estimation of microvessel density, lymphocyte infiltration, and collagen fiber accumulation in the infarcted myocardium was performed 28 days after treatment.Results. Cardiac function was improved, and collagen deposition was decreased significantly after either cell implantation or pravastatin administration alone, but no synergistic effect was seen by their combination. However, microvessel density in the infarcted myocardium was increased only by implantation of bone marrow mononuclear cells, and not by administration of pravastatin. Pravastatin resulted in significant decreases in the serum levels of interleukin 1 beta and tumor necrosis factor-alpha, and also in the infiltration of CD45-positive cells, but not CD117-positive stem cells, in infarcted myocardium. Neither the number of circulating CD34-positive cells nor their endothelial differentiation potency was increased significantly 14 days after oral administration of pravastatin.Conclusions. Pravastatin can improve cardiac function after myocardial infarction, but through an antiinflammatory mechanism, rather than by induction of therapeutic angiogenesis. No synergistic effect for inducing angiogenesis was found by the combination of pravastatin and implantation of bone marrow mononuclear cells.