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Cardioprotective effects of adipokine apelin on myocardial infarction

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Abstract

Angiogenesis plays an important role in myocardial infarction. Apelin and its natural receptor (angiotensin II receptor-like 1, AGTRL-1 or APLNR) induce sprouting of endothelial cells in an autocrine or paracrine manner. The aim of this study is to investigate whether apelin can improve the cardiac function after myocardial infarction by increasing angiogenesis in infarcted myocardium. Left ventricular end-diastolic pressure (LVEDP), left ventricular end systolic pressure (LVESP), left ventricular developed pressure (LVDP), maximal left ventricular pressure development (±LVdp/dtmax), infarct size, and angiogenesis were evaluated to analyze the cardioprotective effects of apelin on ischemic myocardium. Assays of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-bromo-2′-deoxyuridine incorporation, wound healing, transwells, and tube formation were used to detect the effects of apelin on proliferation, migration, and chemotaxis of cardiac microvascular endothelial cells. Fluorescein isothiocyanate-labeled bovine serum albumin penetrating through monolayered cardiac microvascular endothelial cells was measured to evaluate the effects of apelin on permeability of microvascular endothelial cells. In vivo results showed that apelin increased ±LV dp/dtmax and LVESP values, decreased LVEDP values (all p < 0.05), and promoted angiogenesis in rat heart after ligation of the left anterior descending coronary artery. In vitro results showed that apelin dose-dependently enhanced proliferation, migration, chemotaxis, and tube formation, but not permeability of cardiac microvascular endothelial cells. Apelin also increased the expression of vascular endothelial growth factor receptors-2 (VEGFR2) and the endothelium-specific receptor tyrosine kinase (Tie-2) in cardiac microvascular endothelial cells. These results indicated that apelin played a protective role in myocardial infarction through promoting angiogenesis and decreasing permeability of microvascular endothelial cells via upregulating the expression of VEGFR2 and Tie-2 in cardiac microvascular endothelial cells.

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Acknowledgments

This project was supported by the Natural Science Foundation of China (Grant No. 30900573) and Beijing Talents Education Project.

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Authors and Affiliations

  1. The Department of Pathophysiology, Capital Medical University, Beijing, 100069, China

    Bao-Hai Zhang, Hong-Xia Wang, Ling-Qiao Lu, Li-Ke Zhang & Xiang-Jun Zeng

  2. Division of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

    Bao-Hai Zhang, Cai-Xia Guo & Feng-He Du

  3. Laboratory of Clinical Medical Research, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

    Ya-Jie Wang

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  1. Bao-Hai Zhang
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Correspondence to Feng-He Du or Xiang-Jun Zeng.

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B.-H. Zhang and C.-X. Guo contributed equally to this study.

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Zhang, BH., Guo, CX., Wang, HX. et al. Cardioprotective effects of adipokine apelin on myocardial infarction. Heart Vessels 29, 679–689 (2014). https://doi.org/10.1007/s00380-013-0425-z

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  • DOI: https://doi.org/10.1007/s00380-013-0425-z

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