Jacob R. Anderson, Nancy L. Kanagy, Laura V. Gonzalez Bosc, Jay S. Naik
{"title":"剪切应力调节内皮细胞abca1依赖性膜胆固醇含量，促进h2s依赖性血管舒张。","authors":"Jacob R. Anderson, Nancy L. Kanagy, Laura V. Gonzalez Bosc, Jay S. Naik","doi":"10.1111/micc.70029","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <p>Endothelial cells (ECs) express an array of integral membrane proteins, including ion channels and transporters that contribute to blood flow regulation and cell–cell communication. Many of these membrane proteins are regulated by plasma membrane cholesterol content. The ATP-binding cassette family A1 (ABCA1) transporter is a regulator of membrane cholesterol content. We have shown increased ABCA1 mRNA expression and reduced EC membrane cholesterol in resistance mesenteric arteries compared to conduit arteries. Previous studies suggest shear stress (SS) can increase or decrease ABCA1 expression in a cell-type-dependent manner.</p>\n </section>\n \n <section>\n \n <h3> Hypothesis</h3>\n \n <p>SS sustains lower EC membrane cholesterol concentration through ABCA1-mediated cholesterol transport, facilitating H<sub>2</sub>S-mediated vasodilation.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The effect of SS on ABCA1 and membrane cholesterol content was assessed in pressurized mesenteric arteries from male Sprague–Dawley rats and cultured human aortic endothelial cells. Pressure myography was used to assess the effects of ABCA1 inhibition on H<sub>2</sub>S-mediated vasodilation. Filipin was used to assess EC membrane cholesterol content.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>SS increased ABCA1 expression in the endothelium of mesenteric arteries and cultured human aortic endothelial cells and markedly reduced EC membrane cholesterol. Inhibition of ABCA1 increased EC membrane cholesterol content and abolished H<sub>2</sub>S-induced vasodilation.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>SS facilitation of EC-dependent vasodilation appears to be mediated by membrane cholesterol content.</p>\n </section>\n </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498007/pdf/","citationCount":"0","resultStr":"{\"title\":\"Shear Stress Regulates ABCA1-Dependent Membrane Cholesterol Content in Endothelial Cells Facilitating H2S-Dependent Vasodilation\",\"authors\":\"Jacob R. Anderson, Nancy L. Kanagy, Laura V. Gonzalez Bosc, Jay S. Naik\",\"doi\":\"10.1111/micc.70029\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <p>Endothelial cells (ECs) express an array of integral membrane proteins, including ion channels and transporters that contribute to blood flow regulation and cell–cell communication. Many of these membrane proteins are regulated by plasma membrane cholesterol content. The ATP-binding cassette family A1 (ABCA1) transporter is a regulator of membrane cholesterol content. We have shown increased ABCA1 mRNA expression and reduced EC membrane cholesterol in resistance mesenteric arteries compared to conduit arteries. Previous studies suggest shear stress (SS) can increase or decrease ABCA1 expression in a cell-type-dependent manner.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Hypothesis</h3>\\n \\n <p>SS sustains lower EC membrane cholesterol concentration through ABCA1-mediated cholesterol transport, facilitating H<sub>2</sub>S-mediated vasodilation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The effect of SS on ABCA1 and membrane cholesterol content was assessed in pressurized mesenteric arteries from male Sprague–Dawley rats and cultured human aortic endothelial cells. Pressure myography was used to assess the effects of ABCA1 inhibition on H<sub>2</sub>S-mediated vasodilation. Filipin was used to assess EC membrane cholesterol content.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>SS increased ABCA1 expression in the endothelium of mesenteric arteries and cultured human aortic endothelial cells and markedly reduced EC membrane cholesterol. Inhibition of ABCA1 increased EC membrane cholesterol content and abolished H<sub>2</sub>S-induced vasodilation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>SS facilitation of EC-dependent vasodilation appears to be mediated by membrane cholesterol content.</p>\\n </section>\\n </div>\",\"PeriodicalId\":18459,\"journal\":{\"name\":\"Microcirculation\",\"volume\":\"32 7\",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-10-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498007/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microcirculation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/micc.70029\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microcirculation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/micc.70029","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Endothelial cells (ECs) express an array of integral membrane proteins, including ion channels and transporters that contribute to blood flow regulation and cell–cell communication. Many of these membrane proteins are regulated by plasma membrane cholesterol content. The ATP-binding cassette family A1 (ABCA1) transporter is a regulator of membrane cholesterol content. We have shown increased ABCA1 mRNA expression and reduced EC membrane cholesterol in resistance mesenteric arteries compared to conduit arteries. Previous studies suggest shear stress (SS) can increase or decrease ABCA1 expression in a cell-type-dependent manner.
Hypothesis
SS sustains lower EC membrane cholesterol concentration through ABCA1-mediated cholesterol transport, facilitating H2S-mediated vasodilation.
Methods
The effect of SS on ABCA1 and membrane cholesterol content was assessed in pressurized mesenteric arteries from male Sprague–Dawley rats and cultured human aortic endothelial cells. Pressure myography was used to assess the effects of ABCA1 inhibition on H2S-mediated vasodilation. Filipin was used to assess EC membrane cholesterol content.
Results
SS increased ABCA1 expression in the endothelium of mesenteric arteries and cultured human aortic endothelial cells and markedly reduced EC membrane cholesterol. Inhibition of ABCA1 increased EC membrane cholesterol content and abolished H2S-induced vasodilation.
Conclusion
SS facilitation of EC-dependent vasodilation appears to be mediated by membrane cholesterol content.
期刊介绍：
The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation.
Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.
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