Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis

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.

Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure

“…This could account for intercellular cyclic nucleotide signalling, and MRPs constitute prospective drug targets in HF. The hypertrophic and fibrotic actions of AngII are blunted by the PDE1 inhibitor vinpocetine in vitro and in vivo [66], and PDE1i improves cardiac function in failing mouse hearts through greater proteasomal activity [67]. Indeed, the pharmacological and genetic ablation of PDE1 was recently shown to enhance cAMP signalling through the adenosine A 2 receptor (A 2 R), which is protective in multiple models of HF (including in larger mammals, e.g.…”

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

“…Research showed that myocardial fibrosis could be induced by continuous infusion of angiotensin at different rates of 0.2 or 2.0 μg/kg/min (no mice died during the 4 weeks of Ang II infusion) [121], 200 ng/kg/min [122], 1.5 μg/day [123] and 0.83 μg/kg/min [124], 400 ng/kg/min [125], and 0.7 mg/kg/d [126] via an osmotic minipump for 4 weeks. In addition, myocardial fibrosis could also be induced by continuous infusion of angiotensin at the rates of 1.5 mg/kg/day [127], 1000 ng/kg/ min [128], 1.1 mg/kg/day [129],and 800 ng/min/kg [130] via an osmotic minipump for 2 weeks. ese differences may be related to different types of animals and equipment used in experiments.…”

Effectiveness of Cavinton® Comforte (Vinpocetin) in Therapy Patients with Arterial Hypertension, Atherosclerosis and Cerebral Venous Insufficiency

“…Одним из препаратов, обладающим плейотропным действием и широко применяемым для лечения цереброваскулярных заболеваний, является Кавинтон® (действующее вещество -винпоцетин, производство «Гедеон Рихтер», Венгрия). Многочисленные клинические и фундаментальные исследования выявили нейропротективные и вазоактивные эффекты винпоцетина, реализуемые через различные механизмы [13][14][15][16][17]. Однако в проведенных ранее исследованиях при различных формах цереброваскулярной патологии не оценивалось влияние винпоцетина, в частности препарата Кавинтон® Комфорте, на церебральный венозный кровоток.…”