Sun Jiayin, Xie Jun, Kang Lina, Ferro Albert, Dong Li, Xu Biao
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.
Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.
Biomed Res Int. 2016;2016:3182764. doi: 10.1155/2016/3182764. Epub 2016 May 8.
Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI) through improving bone marrow endothelial progenitor cell (EPC) mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg(-1) day(-1)), amlodipine (2.5 mgkg(-1) day(-1)), or vehicle by gavage (n = 20 per group). Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5). Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.
目的。我们研究了氨氯地平是否能像血管紧张素转换酶抑制剂一样，通过改善骨髓内皮祖细胞（EPC）的动员，来改善糖尿病急性心肌梗死（AMI）大鼠模型的血管生成反应。方法。通过冠状动脉结扎诱导AMI后，将糖尿病大鼠随机分为接受培哚普利（2mgkg⁻¹ 天⁻¹）、氨氯地平（2.5mgkg⁻¹ 天⁻¹）或通过灌胃给予赋形剂（每组n = 20）。在每组中测量结扎前以及AMI后第1、3、5、7、14和28天的循环EPC计数。治疗4周后评估微血管密度、心脏功能和心脏重塑。还测量了与EPC动员相关的信号通路。结果。氨氯地平和培哚普利治疗的大鼠循环EPC计数在第7天达到峰值，明显高于对照组较早达到的峰值（第5天）。接受氨氯地平治疗的大鼠缺血后新生血管形成和心脏功能得到改善，同时心脏重塑减轻、间质纤维化减少和心肌细胞凋亡减少。氨氯地平治疗还增加了心脏SDF-1/CXCR4表达，并导致骨髓中VEGF/Akt/eNOS信号通路激活。结论。氨氯地平通过改善AMI后糖尿病大鼠骨髓中EPC的动员来促进新生血管形成，VEGF/Akt/eNOS信号通路的激活可能部分促成了这一点。
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