Expression of functional angiotensin-converting enzyme and AT1 receptors in cultured human cardiac fibroblasts
Angiotensin II (Ang II) has been implicated in the development of cardiac fibrosis. The aims of the present study were to examine expression and activity of ACE and of angiotensin receptors in human cardiac fibroblasts cultured from dilated cardiomyopathic and ischemic hearts. The effects of Ang II...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1998-12, Vol.98 (23), p.2553-2559 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | HAFIZI, S WHARTON, J MORGAN, K ALLEN, S. P CHESTER, A. H CATRAVAS, J. D POLAK, J. M YACOUB, M. H |
| description | Angiotensin II (Ang II) has been implicated in the development of cardiac fibrosis. The aims of the present study were to examine expression and activity of ACE and of angiotensin receptors in human cardiac fibroblasts cultured from dilated cardiomyopathic and ischemic hearts. The effects of Ang II on fibroblasts were also investigated.
Human cardiac fibroblasts were cultured from ventricular and atrial myocardium and characterized immunohistochemically. Expression of ACE and the angiotensin AT1 receptor was demonstrated in cardiac fibroblasts by reverse transcriptase-polymerase chain reaction and radioligand binding. Functional ACE activity, measured by radiolabeled substrate conversion assay, was detected in both ventricular (Vmax. Km-1. mg-1, 0.031+/-0.010; n=13) and atrial (0. 034+/-0.012; n=6) fibroblasts. Fibroblast ACE activity was increased after 48 hours of treatment with basic fibroblast growth factor, dexamethasone, and phorbol ester. Ang II did not affect DNA synthesis but stimulated [3H]proline incorporation in cardiac fibroblasts (20.0+/-4.0% increase above control by 10 micromol/L; P |
| doi_str_mv | 10.1161/01.CIR.98.23.2553 |
| format | Article |
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Human cardiac fibroblasts were cultured from ventricular and atrial myocardium and characterized immunohistochemically. Expression of ACE and the angiotensin AT1 receptor was demonstrated in cardiac fibroblasts by reverse transcriptase-polymerase chain reaction and radioligand binding. Functional ACE activity, measured by radiolabeled substrate conversion assay, was detected in both ventricular (Vmax. Km-1. mg-1, 0.031+/-0.010; n=13) and atrial (0. 034+/-0.012; n=6) fibroblasts. Fibroblast ACE activity was increased after 48 hours of treatment with basic fibroblast growth factor, dexamethasone, and phorbol ester. Ang II did not affect DNA synthesis but stimulated [3H]proline incorporation in cardiac fibroblasts (20.0+/-4.0% increase above control by 10 micromol/L; P<0.05, n=7), which was abolished by losartan 10 micromol/L but not PD123319 1 micromol/L. Ang II also stimulated a rise in intracellular calcium (basal, 56+/-1 nmol/L; Ang II, 355+/-24 nmol/L) via the AT1 receptor, as shown by complete inhibition with losartan.
We have demonstrated expression and activity of ACE and AT1 receptor in cultured human cardiac fibroblasts. In addition, cardiac fibroblasts respond to Ang II with AT1 receptor-mediated collagen synthesis. The presence of local ACE and AT1 receptors in human fibroblasts suggests their involvement in the development of cardiac fibrosis.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.98.23.2553</identifier><identifier>PMID: 9843462</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Biological and medical sciences ; Calcium - metabolism ; Cardiology. Vascular system ; Cells, Cultured ; Fibroblasts - metabolism ; Fibrosis ; Heart ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Humans ; Medical sciences ; Myocardium - metabolism ; Myocardium - pathology ; Peptidyl-Dipeptidase A - biosynthesis ; Receptors, Angiotensin - biosynthesis</subject><ispartof>Circulation (New York, N.Y.), 1998-12, Vol.98 (23), p.2553-2559</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Dec 8, 1998</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1611225$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9843462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HAFIZI, S</creatorcontrib><creatorcontrib>WHARTON, J</creatorcontrib><creatorcontrib>MORGAN, K</creatorcontrib><creatorcontrib>ALLEN, S. P</creatorcontrib><creatorcontrib>CHESTER, A. H</creatorcontrib><creatorcontrib>CATRAVAS, J. D</creatorcontrib><creatorcontrib>POLAK, J. M</creatorcontrib><creatorcontrib>YACOUB, M. H</creatorcontrib><title>Expression of functional angiotensin-converting enzyme and AT1 receptors in cultured human cardiac fibroblasts</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Angiotensin II (Ang II) has been implicated in the development of cardiac fibrosis. The aims of the present study were to examine expression and activity of ACE and of angiotensin receptors in human cardiac fibroblasts cultured from dilated cardiomyopathic and ischemic hearts. The effects of Ang II on fibroblasts were also investigated.
Human cardiac fibroblasts were cultured from ventricular and atrial myocardium and characterized immunohistochemically. Expression of ACE and the angiotensin AT1 receptor was demonstrated in cardiac fibroblasts by reverse transcriptase-polymerase chain reaction and radioligand binding. Functional ACE activity, measured by radiolabeled substrate conversion assay, was detected in both ventricular (Vmax. Km-1. mg-1, 0.031+/-0.010; n=13) and atrial (0. 034+/-0.012; n=6) fibroblasts. Fibroblast ACE activity was increased after 48 hours of treatment with basic fibroblast growth factor, dexamethasone, and phorbol ester. Ang II did not affect DNA synthesis but stimulated [3H]proline incorporation in cardiac fibroblasts (20.0+/-4.0% increase above control by 10 micromol/L; P<0.05, n=7), which was abolished by losartan 10 micromol/L but not PD123319 1 micromol/L. Ang II also stimulated a rise in intracellular calcium (basal, 56+/-1 nmol/L; Ang II, 355+/-24 nmol/L) via the AT1 receptor, as shown by complete inhibition with losartan.
We have demonstrated expression and activity of ACE and AT1 receptor in cultured human cardiac fibroblasts. In addition, cardiac fibroblasts respond to Ang II with AT1 receptor-mediated collagen synthesis. The presence of local ACE and AT1 receptors in human fibroblasts suggests their involvement in the development of cardiac fibrosis.</description><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Fibroblasts - metabolism</subject><subject>Fibrosis</subject><subject>Heart</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Peptidyl-Dipeptidase A - biosynthesis</subject><subject>Receptors, Angiotensin - biosynthesis</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtLxTAQhYMoen38ABdCEHHX2kyS23YpF18gCKLrkqQTjbTJNWlF_fUGvLhwNedwPgbmDCHHrCoZW7KLipWru8eybUrgJUjJt8iCSRCFkLzdJouqqtqi5gB7ZD-lt2yXvJa7ZLdtBBdLWBB_9bmOmJILngZL7ezNlLUaqPIvLkzok_OFCf4D4-T8C0X__TViTnt6-cRoRIPrKcREnadmHqY5Yk9f51Flq2LvlKHW6Rj0oNKUDsmOVUPCo808IM_XV0-r2-L-4eZudXlfvAJrp0IrLTXHpQHbK9Vrm3UjZMN0JaCRuhcNr1G22kowDDUCmhatMciZ6iXjB-T8d-86hvcZ09SNLhkcBuUxzKmrK1bxXEUGT_-Bb2GO-f7UAYMapACRoZMNNOsR-24d3ajiV7dpMednm1wlowYblTcu_WH5UwxA8h-jeYO_</recordid><startdate>19981208</startdate><enddate>19981208</enddate><creator>HAFIZI, S</creator><creator>WHARTON, J</creator><creator>MORGAN, K</creator><creator>ALLEN, S. P</creator><creator>CHESTER, A. H</creator><creator>CATRAVAS, J. D</creator><creator>POLAK, J. M</creator><creator>YACOUB, M. H</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19981208</creationdate><title>Expression of functional angiotensin-converting enzyme and AT1 receptors in cultured human cardiac fibroblasts</title><author>HAFIZI, S ; WHARTON, J ; MORGAN, K ; ALLEN, S. P ; CHESTER, A. H ; CATRAVAS, J. D ; POLAK, J. M ; YACOUB, M. H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h219t-bab5b3e6c2fdaadbf3e684581b04285bd4837e59bf52c1ebe2ec9efcce31ad513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Fibroblasts - metabolism</topic><topic>Fibrosis</topic><topic>Heart</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Peptidyl-Dipeptidase A - biosynthesis</topic><topic>Receptors, Angiotensin - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HAFIZI, S</creatorcontrib><creatorcontrib>WHARTON, J</creatorcontrib><creatorcontrib>MORGAN, K</creatorcontrib><creatorcontrib>ALLEN, S. P</creatorcontrib><creatorcontrib>CHESTER, A. H</creatorcontrib><creatorcontrib>CATRAVAS, J. D</creatorcontrib><creatorcontrib>POLAK, J. M</creatorcontrib><creatorcontrib>YACOUB, M. H</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</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>HAFIZI, S</au><au>WHARTON, J</au><au>MORGAN, K</au><au>ALLEN, S. P</au><au>CHESTER, A. H</au><au>CATRAVAS, J. D</au><au>POLAK, J. M</au><au>YACOUB, M. H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of functional angiotensin-converting enzyme and AT1 receptors in cultured human cardiac fibroblasts</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1998-12-08</date><risdate>1998</risdate><volume>98</volume><issue>23</issue><spage>2553</spage><epage>2559</epage><pages>2553-2559</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Angiotensin II (Ang II) has been implicated in the development of cardiac fibrosis. The aims of the present study were to examine expression and activity of ACE and of angiotensin receptors in human cardiac fibroblasts cultured from dilated cardiomyopathic and ischemic hearts. The effects of Ang II on fibroblasts were also investigated.
Human cardiac fibroblasts were cultured from ventricular and atrial myocardium and characterized immunohistochemically. Expression of ACE and the angiotensin AT1 receptor was demonstrated in cardiac fibroblasts by reverse transcriptase-polymerase chain reaction and radioligand binding. Functional ACE activity, measured by radiolabeled substrate conversion assay, was detected in both ventricular (Vmax. Km-1. mg-1, 0.031+/-0.010; n=13) and atrial (0. 034+/-0.012; n=6) fibroblasts. Fibroblast ACE activity was increased after 48 hours of treatment with basic fibroblast growth factor, dexamethasone, and phorbol ester. Ang II did not affect DNA synthesis but stimulated [3H]proline incorporation in cardiac fibroblasts (20.0+/-4.0% increase above control by 10 micromol/L; P<0.05, n=7), which was abolished by losartan 10 micromol/L but not PD123319 1 micromol/L. Ang II also stimulated a rise in intracellular calcium (basal, 56+/-1 nmol/L; Ang II, 355+/-24 nmol/L) via the AT1 receptor, as shown by complete inhibition with losartan.
We have demonstrated expression and activity of ACE and AT1 receptor in cultured human cardiac fibroblasts. In addition, cardiac fibroblasts respond to Ang II with AT1 receptor-mediated collagen synthesis. The presence of local ACE and AT1 receptors in human fibroblasts suggests their involvement in the development of cardiac fibrosis.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>9843462</pmid><doi>10.1161/01.CIR.98.23.2553</doi><tpages>7</tpages></addata></record> |
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| subjects | Biological and medical sciences Calcium - metabolism Cardiology. Vascular system Cells, Cultured Fibroblasts - metabolism Fibrosis Heart Heart failure, cardiogenic pulmonary edema, cardiac enlargement Humans Medical sciences Myocardium - metabolism Myocardium - pathology Peptidyl-Dipeptidase A - biosynthesis Receptors, Angiotensin - biosynthesis |
| title | Expression of functional angiotensin-converting enzyme and AT1 receptors in cultured human cardiac fibroblasts |
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