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Cardiovascular Drugs and Therapy

, Volume 31, Issue 2, pp 157–166 | Cite as

Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis

  • Mei-ping Wu
  • Yi-shuai Zhang
  • Xiangbin Xu
  • Qian Zhou
  • Jian-Dong Li
  • Chen Yan
ORIGINAL ARTICLE

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.

Keywords

Vinpocetine Cardiac remodeling Cardiac hypertrophy Cardiac fibrosis PDE1 

Notes

Compliance with Ethical Standards

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.

Supplementary material

10557_2017_6719_MOESM1_ESM.pdf (606 kb)
ESM 1 (PDF 605 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Cardiology, Shanghai Municipal Hospital of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
  2. 2.Aab Cardiovascular Research Institute, School of Medicine and DentistryUniversity of RochesterRochesterUSA
  3. 3.Department of Microbiology and ImmunologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  4. 4.Center for Inflammation, Immunity & Infection, Institute for Biomedical SciencesGeorgia State UniversityAtlantaUSA

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