Jill Badin, Stacey Rodenbeck, Mikaela L McKenney-Drake, Michael Sturek
{"title":"冠状动脉粥样硬化过程中平滑肌Ca2+转运蛋白的多相变化。","authors":"Jill Badin, Stacey Rodenbeck, Mikaela L McKenney-Drake, Michael Sturek","doi":"10.1016/bs.ctm.2022.09.007","DOIUrl":null,"url":null,"abstract":"<p><p>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 Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) regulates a variety of cellular functions including contraction, proliferation, migration, and transcription. It follows that studies of vascular Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>, and voltage-gated Ca<sup>2+</sup> 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 Ca<sup>2+</sup> transporters. Overall, there was a biphasic change in Ca<sup>2+</sup> 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 Ca<sup>2+</sup> release occurred through the TPC2 channel. We propose a multiphasic change in Ca<sup>2+</sup> transporters over the progression of coronary atherosclerosis.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"90 ","pages":"95-121"},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multiphasic changes in smooth muscle Ca<sup>2+</sup> transporters during the progression of coronary atherosclerosis.\",\"authors\":\"Jill Badin, Stacey Rodenbeck, Mikaela L McKenney-Drake, Michael Sturek\",\"doi\":\"10.1016/bs.ctm.2022.09.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) regulates a variety of cellular functions including contraction, proliferation, migration, and transcription. It follows that studies of vascular Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>, and voltage-gated Ca<sup>2+</sup> 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 Ca<sup>2+</sup> transporters. Overall, there was a biphasic change in Ca<sup>2+</sup> 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 Ca<sup>2+</sup> release occurred through the TPC2 channel. We propose a multiphasic change in Ca<sup>2+</sup> transporters over the progression of coronary atherosclerosis.</p>\",\"PeriodicalId\":11029,\"journal\":{\"name\":\"Current topics in membranes\",\"volume\":\"90 \",\"pages\":\"95-121\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current topics in membranes\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/bs.ctm.2022.09.007\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in membranes","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.ctm.2022.09.007","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
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.
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.