Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation
The Ca(2+)-activated chloride channel (CaCC) plays an important role in a variety of physiological functions. In vascular smooth muscle cells, CaCC is involved in the regulation of agonist-stimulated contraction and myogenic tone. The physiological functions of CaCC in blood vessels are not fully re...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2012-02, Vol.125 (5), p.697-707 |
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| creator | MI WANG HUI YANG GUAN, Yong-Yuan ZHENG, Ling-Yun ZHENG ZHANG TANG, Yong-Bo WANG, Guan-Lei DU, Yan-Hua LV, Xiao-Fei JIE LIU ZHOU, Jia-Guo |
| description | The Ca(2+)-activated chloride channel (CaCC) plays an important role in a variety of physiological functions. In vascular smooth muscle cells, CaCC is involved in the regulation of agonist-stimulated contraction and myogenic tone. The physiological functions of CaCC in blood vessels are not fully revealed because of the lack of specific channel blockers and the uncertainty concerning its molecular identity.
Whole-cell patch-clamp studies showed that knockdown of TMEM16A but not bestrophin-3 attenuated CaCC currents in rat basilar smooth muscle cells. The activity of CaCC in basilar smooth muscle cells isolated from 2-kidney, 2-clip renohypertensive rats was decreased, and CaCC activity was negatively correlated with blood pressure (n=25; P |
| doi_str_mv | 10.1161/circulationaha.111.041806 |
| format | Article |
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Whole-cell patch-clamp studies showed that knockdown of TMEM16A but not bestrophin-3 attenuated CaCC currents in rat basilar smooth muscle cells. The activity of CaCC in basilar smooth muscle cells isolated from 2-kidney, 2-clip renohypertensive rats was decreased, and CaCC activity was negatively correlated with blood pressure (n=25; P<0.0001) and medial cross-sectional area (n=24; P<0.0001) in basilar artery during hypertension. Both upregulation of CaMKII activity and downregulation of TMEM16A expression contributed to the reduction of CaCC in the hypertensive basilar artery. Western blot results demonstrated that angiotensin II repressed TMEM16A expression in basilar smooth muscle cells (n=6; P<0.01). Knockdown of TMEM16A facilitated and overexpression of TMEM16A inhibited angiotensin II-induced cell cycle transition and cell proliferation determined by flow cytometry and BrdU incorporation (n=6 in each group; P<0.05). TMEM16A affected cell cycle progression mainly through regulating the expression of cyclin D1 and cyclin E.
TMEM16A CaCC is a negative regulator of cell proliferation. Downregulation of CaCC may play an important role in hypertension-induced cerebrovascular remodeling, suggesting that modification of the activity of CaCC may be a novel therapeutic strategy for hypertension-associated cardiovascular diseases such as stroke.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/circulationaha.111.041806</identifier><identifier>PMID: 22215857</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Anoctamin-1 ; Basilar Artery - metabolism ; Basilar Artery - pathology ; Bestrophins ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood vessels and receptors ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism ; Cardiology. Vascular system ; Cell Cycle - physiology ; Cell Proliferation ; Cells, Cultured ; Chloride Channels - metabolism ; Disease Models, Animal ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Down-Regulation ; Fundamental and applied biological sciences. Psychology ; Hypertension - metabolism ; Hypertension - pathology ; Male ; Medical sciences ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - pathology ; Patch-Clamp Techniques ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Sprague-Dawley ; Vertebrates: cardiovascular system</subject><ispartof>Circulation (New York, N.Y.), 2012-02, Vol.125 (5), p.697-707</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-773a776990db01aca5cdc48d3430c20b1700424321230d0f35a6dcde2a489fae3</citedby><cites>FETCH-LOGICAL-c519t-773a776990db01aca5cdc48d3430c20b1700424321230d0f35a6dcde2a489fae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25518488$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22215857$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MI WANG</creatorcontrib><creatorcontrib>HUI YANG</creatorcontrib><creatorcontrib>GUAN, Yong-Yuan</creatorcontrib><creatorcontrib>ZHENG, Ling-Yun</creatorcontrib><creatorcontrib>ZHENG ZHANG</creatorcontrib><creatorcontrib>TANG, Yong-Bo</creatorcontrib><creatorcontrib>WANG, Guan-Lei</creatorcontrib><creatorcontrib>DU, Yan-Hua</creatorcontrib><creatorcontrib>LV, Xiao-Fei</creatorcontrib><creatorcontrib>JIE LIU</creatorcontrib><creatorcontrib>ZHOU, Jia-Guo</creatorcontrib><title>Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The Ca(2+)-activated chloride channel (CaCC) plays an important role in a variety of physiological functions. In vascular smooth muscle cells, CaCC is involved in the regulation of agonist-stimulated contraction and myogenic tone. The physiological functions of CaCC in blood vessels are not fully revealed because of the lack of specific channel blockers and the uncertainty concerning its molecular identity.
Whole-cell patch-clamp studies showed that knockdown of TMEM16A but not bestrophin-3 attenuated CaCC currents in rat basilar smooth muscle cells. The activity of CaCC in basilar smooth muscle cells isolated from 2-kidney, 2-clip renohypertensive rats was decreased, and CaCC activity was negatively correlated with blood pressure (n=25; P<0.0001) and medial cross-sectional area (n=24; P<0.0001) in basilar artery during hypertension. Both upregulation of CaMKII activity and downregulation of TMEM16A expression contributed to the reduction of CaCC in the hypertensive basilar artery. Western blot results demonstrated that angiotensin II repressed TMEM16A expression in basilar smooth muscle cells (n=6; P<0.01). Knockdown of TMEM16A facilitated and overexpression of TMEM16A inhibited angiotensin II-induced cell cycle transition and cell proliferation determined by flow cytometry and BrdU incorporation (n=6 in each group; P<0.05). TMEM16A affected cell cycle progression mainly through regulating the expression of cyclin D1 and cyclin E.
TMEM16A CaCC is a negative regulator of cell proliferation. Downregulation of CaCC may play an important role in hypertension-induced cerebrovascular remodeling, suggesting that modification of the activity of CaCC may be a novel therapeutic strategy for hypertension-associated cardiovascular diseases such as stroke.</description><subject>Animals</subject><subject>Anoctamin-1</subject><subject>Basilar Artery - metabolism</subject><subject>Basilar Artery - pathology</subject><subject>Bestrophins</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood vessels and receptors</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Cell Cycle - physiology</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Chloride Channels - metabolism</subject><subject>Disease Models, Animal</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Down-Regulation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Patch-Clamp Techniques</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Rats, Sprague-Dawley</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc1u1DAUhS1ERYfCKyCzQKxS_JufZUgLM9JMW5XpOnJsp2PkxFPbKZq34hFxmIGurn39nXuPfAD4iNElxjn-Io2XkxXRuFHsROrhS8RwifJXYIE5YRnjtHoNFgihKisoIefgbQg_0zWnBX8DzgkhmJe8WIDfV-7X6PXjaRx0Pdxurjc4r2EjrDTTkNUymmcRtYLNzjpvlE4HMY7awsaN0ZtuijrA6GCjve68exZhtufhvR6c0taMj_Bq8nNZHvbaRz2GeVd3gHfeDS7OL19FMLPmx-Bc3MHNFKRNi7S1M2RNr_1fh-_AWS9s0O9P9QI8fLveNstsfft91dTrTHJcxawoqCiKvKqQ6hAWUnCpJCsVZRRJgjpcIMQIowQTihTqKRe5kkoTwcqqF5pegM_HuXvvniYdYjuYIJMdMWo3hbYiRUkZQSyR1ZGU3oXgdd_uvRmEP7QYtXNebbO6bx7W9XZ1e1Mv69TD7TGvpP1w2jJ1g1b_lf8CSsCnE5A-Vdjei1Ga8MJxjktWlvQPbGak1w</recordid><startdate>20120207</startdate><enddate>20120207</enddate><creator>MI WANG</creator><creator>HUI YANG</creator><creator>GUAN, Yong-Yuan</creator><creator>ZHENG, Ling-Yun</creator><creator>ZHENG ZHANG</creator><creator>TANG, Yong-Bo</creator><creator>WANG, Guan-Lei</creator><creator>DU, Yan-Hua</creator><creator>LV, Xiao-Fei</creator><creator>JIE LIU</creator><creator>ZHOU, Jia-Guo</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120207</creationdate><title>Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation</title><author>MI WANG ; HUI YANG ; GUAN, Yong-Yuan ; ZHENG, Ling-Yun ; ZHENG ZHANG ; TANG, Yong-Bo ; WANG, Guan-Lei ; DU, Yan-Hua ; LV, Xiao-Fei ; JIE LIU ; ZHOU, Jia-Guo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-773a776990db01aca5cdc48d3430c20b1700424321230d0f35a6dcde2a489fae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Anoctamin-1</topic><topic>Basilar Artery - metabolism</topic><topic>Basilar Artery - pathology</topic><topic>Bestrophins</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood vessels and receptors</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Cell Cycle - physiology</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Chloride Channels - metabolism</topic><topic>Disease Models, Animal</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Down-Regulation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hypertension - metabolism</topic><topic>Hypertension - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Patch-Clamp Techniques</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Rats, Sprague-Dawley</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MI WANG</creatorcontrib><creatorcontrib>HUI YANG</creatorcontrib><creatorcontrib>GUAN, Yong-Yuan</creatorcontrib><creatorcontrib>ZHENG, Ling-Yun</creatorcontrib><creatorcontrib>ZHENG ZHANG</creatorcontrib><creatorcontrib>TANG, Yong-Bo</creatorcontrib><creatorcontrib>WANG, Guan-Lei</creatorcontrib><creatorcontrib>DU, Yan-Hua</creatorcontrib><creatorcontrib>LV, Xiao-Fei</creatorcontrib><creatorcontrib>JIE LIU</creatorcontrib><creatorcontrib>ZHOU, Jia-Guo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MI WANG</au><au>HUI YANG</au><au>GUAN, Yong-Yuan</au><au>ZHENG, Ling-Yun</au><au>ZHENG ZHANG</au><au>TANG, Yong-Bo</au><au>WANG, Guan-Lei</au><au>DU, Yan-Hua</au><au>LV, Xiao-Fei</au><au>JIE LIU</au><au>ZHOU, Jia-Guo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2012-02-07</date><risdate>2012</risdate><volume>125</volume><issue>5</issue><spage>697</spage><epage>707</epage><pages>697-707</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The Ca(2+)-activated chloride channel (CaCC) plays an important role in a variety of physiological functions. In vascular smooth muscle cells, CaCC is involved in the regulation of agonist-stimulated contraction and myogenic tone. The physiological functions of CaCC in blood vessels are not fully revealed because of the lack of specific channel blockers and the uncertainty concerning its molecular identity.
Whole-cell patch-clamp studies showed that knockdown of TMEM16A but not bestrophin-3 attenuated CaCC currents in rat basilar smooth muscle cells. The activity of CaCC in basilar smooth muscle cells isolated from 2-kidney, 2-clip renohypertensive rats was decreased, and CaCC activity was negatively correlated with blood pressure (n=25; P<0.0001) and medial cross-sectional area (n=24; P<0.0001) in basilar artery during hypertension. Both upregulation of CaMKII activity and downregulation of TMEM16A expression contributed to the reduction of CaCC in the hypertensive basilar artery. Western blot results demonstrated that angiotensin II repressed TMEM16A expression in basilar smooth muscle cells (n=6; P<0.01). Knockdown of TMEM16A facilitated and overexpression of TMEM16A inhibited angiotensin II-induced cell cycle transition and cell proliferation determined by flow cytometry and BrdU incorporation (n=6 in each group; P<0.05). TMEM16A affected cell cycle progression mainly through regulating the expression of cyclin D1 and cyclin E.
TMEM16A CaCC is a negative regulator of cell proliferation. Downregulation of CaCC may play an important role in hypertension-induced cerebrovascular remodeling, suggesting that modification of the activity of CaCC may be a novel therapeutic strategy for hypertension-associated cardiovascular diseases such as stroke.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>22215857</pmid><doi>10.1161/circulationaha.111.041806</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2012-02, Vol.125 (5), p.697-707 |
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| source | MEDLINE; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals; Journals@Ovid Complete |
| subjects | Animals Anoctamin-1 Basilar Artery - metabolism Basilar Artery - pathology Bestrophins Biological and medical sciences Blood and lymphatic vessels Blood vessels and receptors Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Cardiology. Vascular system Cell Cycle - physiology Cell Proliferation Cells, Cultured Chloride Channels - metabolism Disease Models, Animal Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Down-Regulation Fundamental and applied biological sciences. Psychology Hypertension - metabolism Hypertension - pathology Male Medical sciences Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology Patch-Clamp Techniques Rats Rats, Inbred SHR Rats, Inbred WKY Rats, Sprague-Dawley Vertebrates: cardiovascular system |
| title | Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation |
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