Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis
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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).
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.
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).
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.
KeywordsVinpocetine Cardiac remodeling Cardiac hypertrophy Cardiac fibrosis PDE1
Compliance with Ethical Standards
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.
All procedures performed in studies involving animals were in accordance with ethical standards of the institution or practice at which the studies were conducted.
No human subjects are involved.
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