Long-term exercise training is associated with unique cardiac troponin I phosphorylation pattern and benign myocardial hypertrophy in the right ventricle in an experimental model of exercise-induced myocardial remodelling

IF 4.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology Pub Date : 2025-08-19 DOI:10.1016/j.yjmcc.2025.08.008

Attila Oláh , Beáta Bódi , Bálint András Barta , Olívia Bottlik , Alex Ali Sayour , Mihály Ruppert , Karolina Katarzyna Kolodziejska , Andrea Kovács , Zoltán V. Varga , Péter Ferdinandy , Oliver Schilling , Zoltán Papp , Béla Merkely , Tamás Radovits

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引用次数: 0

Abstract

Background

Research projects have focused on exercise-induced alterations of the right ventricle (RV) of the heart, because the exercise-associated disproportionate load on the RV might lead to pathological consequences, such as interstitial fibrosis, chamber dilation or pro-arrhytmic remodelling. We aimed at providing a complex characterization of RV alterations induced by regular training in a rat model of exercise-induced cardiac remodelling.

Methods

Young, adult rats were divided into control (Co) and exercised (Ex) groups. Exercised rats swam 200 min/day for 12 weeks. In vivo cardiac electrophysiological study and in vitro force measurements on isolated permeabilized RV cardiomyocytes were performed to investigate electrical and functional alterations, respectively. Molecular biological and histological investigations were carried out.

Results

Exercise training was associated with mild increased RV hypertrophy (cardiomyocyte diameter: 12.5 ± 0.1 μm Co vs. 13.7 ± 0.2 μm Ex, p < 0.05) and corresponding hyperphosphorylation of protein kinase B (Akt). Absence of pathological remodelling was revealed by unchanged pro-fibrotic and pro-apoptotic markers. We found increased maximal force development (12.1 ± 1.0kN/m² Co vs. 16.7 ± 1.1 kN/m² Ex, p < 0.05) and improved calcium sensitivity in the cardiomyocytes of exercised animals. Sarcomere protein investigations revealed marked overall and site-specific (Ser22/23, Ser43 and Thr143) hypophosphorylation of troponinI. We found prolonged QT interval (repolarization) and RV effective refracter period along with decreased gene expression of potassium channels. We could not induce any ventricular arrhythmia by programmed stimulation.

Conclusions

Regular swim training induced physiological RV hypertrophy that was associated with functional improvement related to unique hypophosphorilation pattern of troponin I. A balanced exercise program without excessive exercise sessions might not be associated with induction of pathological alterations.

Abstract Image

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在运动诱导心肌重构的实验模型中，长期运动训练与独特的心肌肌钙蛋白I磷酸化模式和右心室良性心肌肥大有关

研究项目主要关注运动引起的右心室（RV）的改变，因为运动相关的右心室不成比例的负荷可能导致病理后果，如间质纤维化、心室扩张或促心律失常重构。我们的目的是在大鼠运动诱导的心脏重构模型中，提供由常规训练引起的右心室改变的复杂特征。方法将幼年、成年大鼠分为对照组（Co）和运动组（Ex）。运动后的大鼠每天游泳200分钟，持续12周。在体内进行心脏电生理研究，并对分离的渗透性心室心肌细胞进行体外力测量，分别研究电和功能的改变。进行了分子生物学和组织学研究。结果运动训练与轻度增加的右心室肥大（心肌细胞直径：12.5±0.1 μm Co vs. 13.7±0.2 μm Ex, p < 0.05）和相应的蛋白激酶B （Akt）高磷酸化相关。未改变的促纤维化和促凋亡标志物显示病理重构的缺失。我们发现运动动物心肌细胞的最大力量发展增加（Co为12.1±1.0kN/m2， Ex为16.7±1.1 kN/m2, p < 0.05），钙敏感性提高。肌瘤蛋白研究显示肌钙蛋白的整体和位点特异性（Ser22/23， Ser43和Thr143）低磷酸化。我们发现QT间期延长（复极）和RV有效折射期随钾通道基因表达减少而延长。程序性刺激不能诱发室性心律失常。结论：定期游泳训练诱导的生理性右心室肥大与肌钙蛋白i独特的低磷酸化模式相关的功能改善有关。没有过度运动的平衡运动计划可能与诱导病理改变无关。

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来源期刊

Journal of molecular and cellular cardiology 医学-细胞生物学

CiteScore

10.70

自引率

0.00%

发文量

171

审稿时长

42 days

期刊介绍： The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; bioengineering; computational modeling and systems analysis; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.