Pioglitazone prevents acute and chronic cardiac allograft rejection
Peroxisome proliferator-activated receptor-gamma plays an important role in regulating inflammation. Although cardiac transplantation is an established therapy for patients with end-stage heart disease, allograft rejection is a major concern for long-term survival. We investigated the role of piogli...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2006-06, Vol.113 (22), p.2613-2622 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | KOSUGE, Hisanori HARAGUCHI, Go KOGA, Noritaka MAEJIMA, Yasuhiro SUZUKI, Jun-Ichi ISOBE, Mitsuaki |
| description | Peroxisome proliferator-activated receptor-gamma plays an important role in regulating inflammation. Although cardiac transplantation is an established therapy for patients with end-stage heart disease, allograft rejection is a major concern for long-term survival. We investigated the role of pioglitazone in acute and chronic rejection in a murine cardiac transplantation model.
We performed heterotopic murine cardiac transplantation in total allomismatch or major histocompatibility complex class II-mismatched combinations. Recipient mice were given standard chow or chow containing pioglitazone (3 mg.kg(-1).d(-1)) beginning 1 day before cardiac transplantation. In acute rejection, animals given pioglitazone showed significantly longer cardiac allograft survival than control mice (mean survival time, 34.6+/-7.8 versus 8.4+/-0.4 days; P |
| doi_str_mv | 10.1161/circulationaha.105.594101 |
| format | Article |
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We performed heterotopic murine cardiac transplantation in total allomismatch or major histocompatibility complex class II-mismatched combinations. Recipient mice were given standard chow or chow containing pioglitazone (3 mg.kg(-1).d(-1)) beginning 1 day before cardiac transplantation. In acute rejection, animals given pioglitazone showed significantly longer cardiac allograft survival than control mice (mean survival time, 34.6+/-7.8 versus 8.4+/-0.4 days; P<0.003). Treatment with pioglitazone significantly suppressed graft expression of interferon-gamma and monocyte chemoattractant protein-1. In chronic rejection, neointimal hyperplasia was significantly lower in allografts from mice treated with pioglitazone (luminal occlusion, 25.1+/-8.8%) than in those from control mice (65.8+/-7.3%, P<0.001). Pioglitazone-treated allografts showed significantly reduced expression of interferon-gamma, interleukin-10, and monocyte chemoattractant protein-1. We performed mixed lymphocyte reactions and in vitro proliferation assays of smooth muscle cells. Addition of pioglitazone to mixed lymphocyte reactions inhibited proliferation of T cells. Smooth muscle cells showed significant proliferation when cocultured with activated splenocytes. This proliferation was significantly inhibited by the addition of pioglitazone (1 micromol/L).
Pioglitazone prolongs allograft survival and attenuates neointimal hyperplasia through the suppression of proliferation of smooth muscle cells. Pioglitazone may be a novel means to prevent acute and chronic allograft rejection.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/circulationaha.105.594101</identifier><identifier>PMID: 16735678</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Proliferation - drug effects ; Cells, Cultured ; Chemokine CCL2 - analysis ; Chemokine CCL2 - genetics ; Chemokine CCL2 - physiology ; Coronary heart disease ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Gene Expression Regulation ; Graft Rejection - drug therapy ; Graft Rejection - pathology ; Graft Rejection - physiopathology ; Graft Rejection - prevention & control ; Graft Survival ; Heart ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Heart Transplantation - pathology ; Heart Transplantation - physiology ; Hyperplasia - pathology ; Hyperplasia - physiopathology ; Hyperplasia - prevention & control ; Interferon-gamma - analysis ; Interferon-gamma - genetics ; Interferon-gamma - physiology ; Interleukin-10 - analysis ; Interleukin-10 - genetics ; Interleukin-10 - physiology ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Myocardium - chemistry ; Myocardium - pathology ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - pathology ; Myocytes, Smooth Muscle - physiology ; PPAR gamma - agonists ; PPAR gamma - physiology ; T-Lymphocytes - pathology ; Thiazolidinediones - pharmacology ; Thiazolidinediones - therapeutic use ; Transplantation, Homologous</subject><ispartof>Circulation (New York, N.Y.), 2006-06, Vol.113 (22), p.2613-2622</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-6a6122e8198b56782798327ff58ba09ae985bcc649ef7be9d16cac0ab8f4d9f43</citedby><cites>FETCH-LOGICAL-c505t-6a6122e8198b56782798327ff58ba09ae985bcc649ef7be9d16cac0ab8f4d9f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17847994$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16735678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KOSUGE, Hisanori</creatorcontrib><creatorcontrib>HARAGUCHI, Go</creatorcontrib><creatorcontrib>KOGA, Noritaka</creatorcontrib><creatorcontrib>MAEJIMA, Yasuhiro</creatorcontrib><creatorcontrib>SUZUKI, Jun-Ichi</creatorcontrib><creatorcontrib>ISOBE, Mitsuaki</creatorcontrib><title>Pioglitazone prevents acute and chronic cardiac allograft rejection</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Peroxisome proliferator-activated receptor-gamma plays an important role in regulating inflammation. Although cardiac transplantation is an established therapy for patients with end-stage heart disease, allograft rejection is a major concern for long-term survival. We investigated the role of pioglitazone in acute and chronic rejection in a murine cardiac transplantation model.
We performed heterotopic murine cardiac transplantation in total allomismatch or major histocompatibility complex class II-mismatched combinations. Recipient mice were given standard chow or chow containing pioglitazone (3 mg.kg(-1).d(-1)) beginning 1 day before cardiac transplantation. In acute rejection, animals given pioglitazone showed significantly longer cardiac allograft survival than control mice (mean survival time, 34.6+/-7.8 versus 8.4+/-0.4 days; P<0.003). Treatment with pioglitazone significantly suppressed graft expression of interferon-gamma and monocyte chemoattractant protein-1. In chronic rejection, neointimal hyperplasia was significantly lower in allografts from mice treated with pioglitazone (luminal occlusion, 25.1+/-8.8%) than in those from control mice (65.8+/-7.3%, P<0.001). Pioglitazone-treated allografts showed significantly reduced expression of interferon-gamma, interleukin-10, and monocyte chemoattractant protein-1. We performed mixed lymphocyte reactions and in vitro proliferation assays of smooth muscle cells. Addition of pioglitazone to mixed lymphocyte reactions inhibited proliferation of T cells. Smooth muscle cells showed significant proliferation when cocultured with activated splenocytes. This proliferation was significantly inhibited by the addition of pioglitazone (1 micromol/L).
Pioglitazone prolongs allograft survival and attenuates neointimal hyperplasia through the suppression of proliferation of smooth muscle cells. Pioglitazone may be a novel means to prevent acute and chronic allograft rejection.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Chemokine CCL2 - analysis</subject><subject>Chemokine CCL2 - genetics</subject><subject>Chemokine CCL2 - physiology</subject><subject>Coronary heart disease</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Gene Expression Regulation</subject><subject>Graft Rejection - drug therapy</subject><subject>Graft Rejection - pathology</subject><subject>Graft Rejection - physiopathology</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival</subject><subject>Heart</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Heart Transplantation - pathology</subject><subject>Heart Transplantation - physiology</subject><subject>Hyperplasia - pathology</subject><subject>Hyperplasia - physiopathology</subject><subject>Hyperplasia - prevention & control</subject><subject>Interferon-gamma - analysis</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - physiology</subject><subject>Interleukin-10 - analysis</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-10 - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Myocardium - chemistry</subject><subject>Myocardium - pathology</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Myocytes, Smooth Muscle - physiology</subject><subject>PPAR gamma - agonists</subject><subject>PPAR gamma - physiology</subject><subject>T-Lymphocytes - pathology</subject><subject>Thiazolidinediones - pharmacology</subject><subject>Thiazolidinediones - therapeutic use</subject><subject>Transplantation, Homologous</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkFtLw0AQhRdRtF7-gsQHfUvdTfb6WILaQrEi9TlMJru6kiZ1NxH015vSgk_DDN-ZcziE3DA6ZUyye_QBhwZ637XwAVNGxVQYzig7IhMmMp5ykZtjMqGUmlTlWXZGzmP8HFeZK3FKzphUuZBKT0jx4rv3xvfw27U22Qb7bds-JoBDbxNo6wQ_Qtd6TBBC7QETaJruPYDrk2A_Le4yXJITB020V4d5Qd4eH9bFPF2unhbFbJmioKJPJUiWZVYzo6udeaaMzjPlnNAVUAPWaFEhSm6sU5U1NZMISKHSjtfG8fyC3O3_bkP3NdjYlxsf0TYNtLYbYik15UJrNYJmD2LoYgzWldvgNxB-SkbLXYNlsXgt3paz9WL1PJvPxrMo9w2O2uuDyVBtbP2vPFQ2ArcHACJC4wK06OM_pzRXxvD8DyPAfYI</recordid><startdate>20060606</startdate><enddate>20060606</enddate><creator>KOSUGE, Hisanori</creator><creator>HARAGUCHI, Go</creator><creator>KOGA, Noritaka</creator><creator>MAEJIMA, Yasuhiro</creator><creator>SUZUKI, Jun-Ichi</creator><creator>ISOBE, Mitsuaki</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>20060606</creationdate><title>Pioglitazone prevents acute and chronic cardiac allograft rejection</title><author>KOSUGE, Hisanori ; HARAGUCHI, Go ; KOGA, Noritaka ; MAEJIMA, Yasuhiro ; SUZUKI, Jun-Ichi ; ISOBE, Mitsuaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-6a6122e8198b56782798327ff58ba09ae985bcc649ef7be9d16cac0ab8f4d9f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Chemokine CCL2 - analysis</topic><topic>Chemokine CCL2 - genetics</topic><topic>Chemokine CCL2 - physiology</topic><topic>Coronary heart disease</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Gene Expression Regulation</topic><topic>Graft Rejection - drug therapy</topic><topic>Graft Rejection - pathology</topic><topic>Graft Rejection - physiopathology</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival</topic><topic>Heart</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Heart Transplantation - pathology</topic><topic>Heart Transplantation - physiology</topic><topic>Hyperplasia - pathology</topic><topic>Hyperplasia - physiopathology</topic><topic>Hyperplasia - prevention & control</topic><topic>Interferon-gamma - analysis</topic><topic>Interferon-gamma - genetics</topic><topic>Interferon-gamma - physiology</topic><topic>Interleukin-10 - analysis</topic><topic>Interleukin-10 - genetics</topic><topic>Interleukin-10 - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Myocardium - chemistry</topic><topic>Myocardium - pathology</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - pathology</topic><topic>Myocytes, Smooth Muscle - physiology</topic><topic>PPAR gamma - agonists</topic><topic>PPAR gamma - physiology</topic><topic>T-Lymphocytes - pathology</topic><topic>Thiazolidinediones - pharmacology</topic><topic>Thiazolidinediones - therapeutic use</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KOSUGE, Hisanori</creatorcontrib><creatorcontrib>HARAGUCHI, Go</creatorcontrib><creatorcontrib>KOGA, Noritaka</creatorcontrib><creatorcontrib>MAEJIMA, Yasuhiro</creatorcontrib><creatorcontrib>SUZUKI, Jun-Ichi</creatorcontrib><creatorcontrib>ISOBE, Mitsuaki</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>KOSUGE, Hisanori</au><au>HARAGUCHI, Go</au><au>KOGA, Noritaka</au><au>MAEJIMA, Yasuhiro</au><au>SUZUKI, Jun-Ichi</au><au>ISOBE, Mitsuaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pioglitazone prevents acute and chronic cardiac allograft rejection</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2006-06-06</date><risdate>2006</risdate><volume>113</volume><issue>22</issue><spage>2613</spage><epage>2622</epage><pages>2613-2622</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Peroxisome proliferator-activated receptor-gamma plays an important role in regulating inflammation. Although cardiac transplantation is an established therapy for patients with end-stage heart disease, allograft rejection is a major concern for long-term survival. We investigated the role of pioglitazone in acute and chronic rejection in a murine cardiac transplantation model.
We performed heterotopic murine cardiac transplantation in total allomismatch or major histocompatibility complex class II-mismatched combinations. Recipient mice were given standard chow or chow containing pioglitazone (3 mg.kg(-1).d(-1)) beginning 1 day before cardiac transplantation. In acute rejection, animals given pioglitazone showed significantly longer cardiac allograft survival than control mice (mean survival time, 34.6+/-7.8 versus 8.4+/-0.4 days; P<0.003). Treatment with pioglitazone significantly suppressed graft expression of interferon-gamma and monocyte chemoattractant protein-1. In chronic rejection, neointimal hyperplasia was significantly lower in allografts from mice treated with pioglitazone (luminal occlusion, 25.1+/-8.8%) than in those from control mice (65.8+/-7.3%, P<0.001). Pioglitazone-treated allografts showed significantly reduced expression of interferon-gamma, interleukin-10, and monocyte chemoattractant protein-1. We performed mixed lymphocyte reactions and in vitro proliferation assays of smooth muscle cells. Addition of pioglitazone to mixed lymphocyte reactions inhibited proliferation of T cells. Smooth muscle cells showed significant proliferation when cocultured with activated splenocytes. This proliferation was significantly inhibited by the addition of pioglitazone (1 micromol/L).
Pioglitazone prolongs allograft survival and attenuates neointimal hyperplasia through the suppression of proliferation of smooth muscle cells. Pioglitazone may be a novel means to prevent acute and chronic allograft rejection.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>16735678</pmid><doi>10.1161/circulationaha.105.594101</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2006-06, Vol.113 (22), p.2613-2622 |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Animals Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Proliferation - drug effects Cells, Cultured Chemokine CCL2 - analysis Chemokine CCL2 - genetics Chemokine CCL2 - physiology Coronary heart disease Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Gene Expression Regulation Graft Rejection - drug therapy Graft Rejection - pathology Graft Rejection - physiopathology Graft Rejection - prevention & control Graft Survival Heart Heart failure, cardiogenic pulmonary edema, cardiac enlargement Heart Transplantation - pathology Heart Transplantation - physiology Hyperplasia - pathology Hyperplasia - physiopathology Hyperplasia - prevention & control Interferon-gamma - analysis Interferon-gamma - genetics Interferon-gamma - physiology Interleukin-10 - analysis Interleukin-10 - genetics Interleukin-10 - physiology Male Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Myocardium - chemistry Myocardium - pathology Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - pathology Myocytes, Smooth Muscle - physiology PPAR gamma - agonists PPAR gamma - physiology T-Lymphocytes - pathology Thiazolidinediones - pharmacology Thiazolidinediones - therapeutic use Transplantation, Homologous |
| title | Pioglitazone prevents acute and chronic cardiac allograft rejection |
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