早期高胆固醇血症诱导的离体心肌细胞电收缩重塑

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-08-01 Epub Date: 2024-06-13 DOI:10.1007/s10863-024-10026-x
Artur Santos-Miranda, Julliane V Joviano-Santos, Ivan Lobo Sousa Marques, Stefany Cau, Fabrício A Carvalho, Júlia R Fraga, Jacqueline I Alvarez-Leite, Danilo Roman-Campos, Jader S Cruz
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引用次数: 0

摘要

高胆固醇血症是心血管疾病最重要的危险因素之一。然而,高胆固醇血症主要与血管功能障碍和动脉粥样硬化病变有关,而高胆固醇血症对心肌细胞和心脏功能直接影响的证据尚不完整,且存在争议。在这项研究中,我们评估了高胆固醇血症对心脏功能和离体心肌细胞电收缩特性的直接影响。用添加了 1.25% 胆固醇(CHO)的 AIN-93 食物喂养雄性瑞士小鼠 5 周后,小鼠血清总胆固醇水平和心肌细胞胆固醇含量增加。这些变化导致心电图记录改变,QT 间期缩短。隔离的心肌细胞显示动作电位持续时间缩短,去极化速率增加,其原因是 IK 增加、ICa.L 减少和 INa 电压依赖性失活改变。此外,在肾上腺素能反应和细胞收缩功能保持不变的情况下,舒张压[Ca2+]i也有所降低。然而,在缺血/再灌注前后,离体 CHO 心脏的收缩功能受损,尽管 CHO 心脏不易发生心律失常性收缩。总之,我们的研究结果表明,早期高胆固醇血症驱动的细胞胆固醇含量增加与直接调节心脏和心肌细胞的兴奋性、Ca2+ 处理和收缩有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Electrocontractile remodeling of isolated cardiomyocytes induced during early-stage hypercholesterolemia.

Electrocontractile remodeling of isolated cardiomyocytes induced during early-stage hypercholesterolemia.

Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased IK, reduced ICa.L and altered INa voltage-dependent inactivation. Also, reduced diastolic [Ca2+]i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca2+ handling, and contraction.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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