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Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis

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Abstract

Purpose

Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II).

Methods

Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts.

Results

We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1).

Conclusions

Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling.

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Author notes

    Authors and Affiliations

    1. Department of Cardiology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China

      Mei-ping Wu & Chen Yan

    2. Aab Cardiovascular Research Institute, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Ave, Box CVRI, Rochester, NY, 14642, USA

      Mei-ping Wu, Yi-shuai Zhang, Qian Zhou & Chen Yan

    3. Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA

      Xiangbin Xu

    4. Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30302, USA

      Jian-Dong Li

    Authors
    1. Mei-ping Wu
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    2. Yi-shuai Zhang
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    5. Jian-Dong Li
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    Corresponding authors

    Correspondence to Jian-Dong Li or Chen Yan.

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    Funding

    This study was supported by grants from National Natural Science Foundation of China No.81473379 and No.81673915 (to M. Wu), No. 81570248 (to C. Y.), Shanghai Municipal Bureau of Health Science and Technology Project No. 2011L032B (to M. Wu), the National Institutes of Health National Heart, Lung, and Blood Institute [Grants HL111291; HL088400 (to C.Y.) and DC005843, DC004562, and DC013833 (to J.D. Li)].

    Conflict of Interest

    The authors declare that they have no conflict of interests.

    Ethical Approval

    All procedures performed in studies involving animals were in accordance with ethical standards of the institution or practice at which the studies were conducted.

    Informed Consent

    No human subjects are involved.

    Additional information

    Mei-ping Wu and Yi-shuai Zhang contributed equally to this work.

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    Wu, Mp., Zhang, Ys., Xu, X. et al. Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis. Cardiovasc Drugs Ther 31, 157–166 (2017). https://doi.org/10.1007/s10557-017-6719-0

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    • DOI: https://doi.org/10.1007/s10557-017-6719-0

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