冠状动脉粥样硬化过程中平滑肌Ca2+转运蛋白的多相变化。

4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Current topics in membranes Pub Date : 2022-01-01 DOI:10.1016/bs.ctm.2022.09.007
Jill Badin, Stacey Rodenbeck, Mikaela L McKenney-Drake, Michael Sturek
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引用次数: 0

摘要

由大血管动脉粥样硬化和微血管功能障碍引起的缺血性心脏病是世界范围内死亡的主要原因,代谢综合征的持续增加是这种情况将继续下去的主要原因。胞内游离Ca2+ ([Ca2+]i)调节多种细胞功能,包括收缩、增殖、迁移和转录。因此,在还原论模型和翻译动物模型中研究血管Ca2+调节对于理解血管健康和疾病至关重要。猪代谢综合征(MetS)发展冠状动脉粥样硬化从轻微到严重的疾病。血管内成像可以在体内定量测量动脉粥样硬化,因此可以将活的冠状动脉平滑肌(CSM)细胞从动脉中分散开来,以便在原生细胞中进行Ca2+运输研究。CSM从健康猪的收缩表型向轻度动脉粥样硬化的增殖表型的转变与SERCA活性、肌浆网Ca2+和电压门控Ca2+通道功能的增加有关。体外器官培养证实,SERCA激活可诱导CSM增殖。从增生性到更成骨表型的转变与所有三种Ca2+转运蛋白的减少有关。总的来说,在猪模型中,Ca2+转运蛋白在动脉粥样硬化的进展过程中存在双相变化,这在人类移植心脏失败的CSM中得到了证实。人CSM内溶酶体含量的主要决定因素是动脉粥样硬化的严重程度。猪CSM内溶酶体Ca2+通过TPC2通道释放。我们提出Ca2+转运蛋白在冠状动脉粥样硬化过程中的多相变化。
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Multiphasic changes in smooth muscle Ca2+ transporters during the progression of coronary atherosclerosis.

Ischemic heart disease due to macrovascular atherosclerosis and microvascular dysfunction is the major cause of death worldwide and the unabated increase in metabolic syndrome is a major reason why this will continue. Intracellular free Ca2+ ([Ca2+]i) regulates a variety of cellular functions including contraction, proliferation, migration, and transcription. It follows that studies of vascular Ca2+ regulation in reductionist models and translational animal models are vital to understanding vascular health and disease. Swine with metabolic syndrome (MetS) develop the full range of coronary atherosclerosis from mild to severe disease. Intravascular imaging enables quantitative measurement of atherosclerosis in vivo, so viable coronary smooth muscle (CSM) cells can be dispersed from the arteries to enable Ca2+ transport studies in native cells. Transition of CSM from the contractile phenotype in the healthy swine to the proliferative phenotype in mild atherosclerosis was associated with increases in SERCA activity, sarcoplasmic reticulum Ca2+, and voltage-gated Ca2+ channel function. In vitro organ culture confirmed that SERCA activation induces CSM proliferation. Transition from the proliferative to a more osteogenic phenotype was associated with decreases in all three Ca2+ transporters. Overall, there was a biphasic change in Ca2+ transporters over the progression of atherosclerosis in the swine model and this was confirmed in CSM from failing explanted hearts of humans. A major determinant of endolysosome content in human CSM is the severity of atherosclerosis. In swine CSM endolysosome Ca2+ release occurred through the TPC2 channel. We propose a multiphasic change in Ca2+ transporters over the progression of coronary atherosclerosis.

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来源期刊
Current topics in membranes
Current topics in membranes 生物-生化与分子生物学
CiteScore
3.50
自引率
0.00%
发文量
10
审稿时长
>12 weeks
期刊介绍: Current Topics in Membranes provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology.
期刊最新文献
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