Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart
Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated β-adrenergic receptor signalling and function on the over...
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| Veröffentlicht in: | Cardiovascular research 2008-05, Vol.78 (2), p.385-394 |
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| creator | Leosco, Dario Rengo, Giuseppe Iaccarino, Guido Golino, Luca Marchese, Massimo Fortunato, Francesca Zincarelli, Carmela Sanzari, Emma Ciccarelli, Michele Galasso, Gennaro Altobelli, Giovanna Giuseppina Conti, Valeria Matrone, Gianfranco Cimini, Vincenzo Ferrara, Nicola Filippelli, Amelia Koch, Walter J. Rengo, Franco |
| description | Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated β-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 ± 5%), increased LV end diastolic pressure (20.9 ± 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac β-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF. |
| doi_str_mv | 10.1093/cvr/cvm109 |
| format | Article |
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We also explored the contribution of ameliorated β-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 ± 5%), increased LV end diastolic pressure (20.9 ± 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac β-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1093/cvr/cvm109</identifier><identifier>PMID: 18093988</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adrenergic beta-Agonists - pharmacology ; Angiogenesis ; Animals ; Coronary Circulation ; Coronary Vessels - drug effects ; Coronary Vessels - metabolism ; Coronary Vessels - physiopathology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Exercise training ; Heart failure ; Heart Failure - diagnostic imaging ; Heart Failure - etiology ; Heart Failure - metabolism ; Heart Failure - physiopathology ; Isoproterenol - pharmacology ; Male ; Myocardial Contraction ; Myocardial Infarction - complications ; Myocardial Infarction - diagnostic imaging ; Myocardial Infarction - metabolism ; Myocardial Infarction - physiopathology ; Myocardium - enzymology ; Myocardium - metabolism ; Myocardium - pathology ; Neovascularization, Physiologic - drug effects ; Nitric Oxide Synthase Type II - metabolism ; Nitric Oxide Synthase Type III ; Physical Exertion ; Proto-Oncogene Proteins c-akt - metabolism ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta - drug effects ; Receptors, Adrenergic, beta - metabolism ; Signal Transduction - drug effects ; Time Factors ; Ultrasonography ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism ; Ventricular Function, Left ; Ventricular Remodeling ; β-adrenergic receptor</subject><ispartof>Cardiovascular research, 2008-05, Vol.78 (2), p.385-394</ispartof><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-4c6af3c58a2dc2b69844c077edc30530dd184e8a8448a813910cf3d6b5e2e83d3</citedby><cites>FETCH-LOGICAL-c389t-4c6af3c58a2dc2b69844c077edc30530dd184e8a8448a813910cf3d6b5e2e83d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18093988$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leosco, Dario</creatorcontrib><creatorcontrib>Rengo, Giuseppe</creatorcontrib><creatorcontrib>Iaccarino, Guido</creatorcontrib><creatorcontrib>Golino, Luca</creatorcontrib><creatorcontrib>Marchese, Massimo</creatorcontrib><creatorcontrib>Fortunato, Francesca</creatorcontrib><creatorcontrib>Zincarelli, Carmela</creatorcontrib><creatorcontrib>Sanzari, Emma</creatorcontrib><creatorcontrib>Ciccarelli, Michele</creatorcontrib><creatorcontrib>Galasso, Gennaro</creatorcontrib><creatorcontrib>Altobelli, Giovanna Giuseppina</creatorcontrib><creatorcontrib>Conti, Valeria</creatorcontrib><creatorcontrib>Matrone, Gianfranco</creatorcontrib><creatorcontrib>Cimini, Vincenzo</creatorcontrib><creatorcontrib>Ferrara, Nicola</creatorcontrib><creatorcontrib>Filippelli, Amelia</creatorcontrib><creatorcontrib>Koch, Walter J.</creatorcontrib><creatorcontrib>Rengo, Franco</creatorcontrib><title>Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated β-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 ± 5%), increased LV end diastolic pressure (20.9 ± 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac β-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.</description><subject>Adrenergic beta-Agonists - pharmacology</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Coronary Circulation</subject><subject>Coronary Vessels - drug effects</subject><subject>Coronary Vessels - metabolism</subject><subject>Coronary Vessels - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Exercise training</subject><subject>Heart failure</subject><subject>Heart Failure - diagnostic imaging</subject><subject>Heart Failure - etiology</subject><subject>Heart Failure - metabolism</subject><subject>Heart Failure - physiopathology</subject><subject>Isoproterenol - pharmacology</subject><subject>Male</subject><subject>Myocardial Contraction</subject><subject>Myocardial Infarction - complications</subject><subject>Myocardial Infarction - diagnostic imaging</subject><subject>Myocardial Infarction - metabolism</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Myocardium - enzymology</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Nitric Oxide Synthase Type III</subject><subject>Physical Exertion</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Adrenergic, beta - drug effects</subject><subject>Receptors, Adrenergic, beta - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Time Factors</subject><subject>Ultrasonography</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Ventricular Function, Left</subject><subject>Ventricular Remodeling</subject><subject>β-adrenergic receptor</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1O3DAUhS3UqgzTbniAKpuyQArYcZw4ywrxJ0ZiM0ioG8tj32Rc8oftIHgtHqTPxIWM2l0Xvvb1-Xx0fQg5ZPSE0YqfmiePq8PzHlmwUoiUZ7n4RBaUUpkWvOD75CCE39gKUeZfyD6T-K6SckGm82fwxgVIRj90Q4SQ6L5xQwM9BPfe2MR1qD2h8uc11daj4htnEg8Gxjj4JLim123r-iZxfRK36DWEmLpgtho6JGvtPlSvY7IF7eNX8rnWbYBvu31J7i7O12dX6er28vrs5yo1XFYxzU2ha26E1Jk12aaoZJ4bWpZgDaeCU2uZzEFqvMbCeMWoqbktNgIykNzyJTmaffEDjxOEqDqcCtpW9zBMQZU0r0RWVAgez6DxQwgeajV612n_ohhV7yErDFnNISP8fec6bTqw_9Bdqgj8mIFhGv9vlM6cCxGe_5LaP6ii5KVQV_e_VJazbH2xvlE3_A33xpfj</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Leosco, Dario</creator><creator>Rengo, Giuseppe</creator><creator>Iaccarino, Guido</creator><creator>Golino, Luca</creator><creator>Marchese, Massimo</creator><creator>Fortunato, Francesca</creator><creator>Zincarelli, Carmela</creator><creator>Sanzari, Emma</creator><creator>Ciccarelli, Michele</creator><creator>Galasso, Gennaro</creator><creator>Altobelli, Giovanna Giuseppina</creator><creator>Conti, Valeria</creator><creator>Matrone, Gianfranco</creator><creator>Cimini, Vincenzo</creator><creator>Ferrara, Nicola</creator><creator>Filippelli, Amelia</creator><creator>Koch, Walter J.</creator><creator>Rengo, Franco</creator><general>Oxford University Press</general><scope>BSCLL</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>20080501</creationdate><title>Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart</title><author>Leosco, Dario ; Rengo, Giuseppe ; Iaccarino, Guido ; Golino, Luca ; Marchese, Massimo ; Fortunato, Francesca ; Zincarelli, Carmela ; Sanzari, Emma ; Ciccarelli, Michele ; Galasso, Gennaro ; Altobelli, Giovanna Giuseppina ; Conti, Valeria ; Matrone, Gianfranco ; Cimini, Vincenzo ; Ferrara, Nicola ; Filippelli, Amelia ; Koch, Walter J. ; Rengo, Franco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-4c6af3c58a2dc2b69844c077edc30530dd184e8a8448a813910cf3d6b5e2e83d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adrenergic beta-Agonists - pharmacology</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Coronary Circulation</topic><topic>Coronary Vessels - drug effects</topic><topic>Coronary Vessels - metabolism</topic><topic>Coronary Vessels - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Exercise training</topic><topic>Heart failure</topic><topic>Heart Failure - diagnostic imaging</topic><topic>Heart Failure - etiology</topic><topic>Heart Failure - metabolism</topic><topic>Heart Failure - physiopathology</topic><topic>Isoproterenol - pharmacology</topic><topic>Male</topic><topic>Myocardial Contraction</topic><topic>Myocardial Infarction - complications</topic><topic>Myocardial Infarction - diagnostic imaging</topic><topic>Myocardial Infarction - metabolism</topic><topic>Myocardial Infarction - physiopathology</topic><topic>Myocardium - enzymology</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Nitric Oxide Synthase Type III</topic><topic>Physical Exertion</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Adrenergic, beta - drug effects</topic><topic>Receptors, Adrenergic, beta - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Time Factors</topic><topic>Ultrasonography</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Ventricular Function, Left</topic><topic>Ventricular Remodeling</topic><topic>β-adrenergic receptor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leosco, Dario</creatorcontrib><creatorcontrib>Rengo, Giuseppe</creatorcontrib><creatorcontrib>Iaccarino, Guido</creatorcontrib><creatorcontrib>Golino, Luca</creatorcontrib><creatorcontrib>Marchese, Massimo</creatorcontrib><creatorcontrib>Fortunato, Francesca</creatorcontrib><creatorcontrib>Zincarelli, Carmela</creatorcontrib><creatorcontrib>Sanzari, Emma</creatorcontrib><creatorcontrib>Ciccarelli, Michele</creatorcontrib><creatorcontrib>Galasso, Gennaro</creatorcontrib><creatorcontrib>Altobelli, Giovanna Giuseppina</creatorcontrib><creatorcontrib>Conti, Valeria</creatorcontrib><creatorcontrib>Matrone, Gianfranco</creatorcontrib><creatorcontrib>Cimini, Vincenzo</creatorcontrib><creatorcontrib>Ferrara, Nicola</creatorcontrib><creatorcontrib>Filippelli, Amelia</creatorcontrib><creatorcontrib>Koch, Walter J.</creatorcontrib><creatorcontrib>Rengo, Franco</creatorcontrib><collection>Istex</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>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leosco, Dario</au><au>Rengo, Giuseppe</au><au>Iaccarino, Guido</au><au>Golino, Luca</au><au>Marchese, Massimo</au><au>Fortunato, Francesca</au><au>Zincarelli, Carmela</au><au>Sanzari, Emma</au><au>Ciccarelli, Michele</au><au>Galasso, Gennaro</au><au>Altobelli, Giovanna Giuseppina</au><au>Conti, Valeria</au><au>Matrone, Gianfranco</au><au>Cimini, Vincenzo</au><au>Ferrara, Nicola</au><au>Filippelli, Amelia</au><au>Koch, Walter J.</au><au>Rengo, Franco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>78</volume><issue>2</issue><spage>385</spage><epage>394</epage><pages>385-394</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><abstract>Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated β-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 ± 5%), increased LV end diastolic pressure (20.9 ± 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac β-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>18093988</pmid><doi>10.1093/cvr/cvm109</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adrenergic beta-Agonists - pharmacology Angiogenesis Animals Coronary Circulation Coronary Vessels - drug effects Coronary Vessels - metabolism Coronary Vessels - physiopathology Disease Models, Animal Dose-Response Relationship, Drug Exercise training Heart failure Heart Failure - diagnostic imaging Heart Failure - etiology Heart Failure - metabolism Heart Failure - physiopathology Isoproterenol - pharmacology Male Myocardial Contraction Myocardial Infarction - complications Myocardial Infarction - diagnostic imaging Myocardial Infarction - metabolism Myocardial Infarction - physiopathology Myocardium - enzymology Myocardium - metabolism Myocardium - pathology Neovascularization, Physiologic - drug effects Nitric Oxide Synthase Type II - metabolism Nitric Oxide Synthase Type III Physical Exertion Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Wistar Receptors, Adrenergic, beta - drug effects Receptors, Adrenergic, beta - metabolism Signal Transduction - drug effects Time Factors Ultrasonography Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism Ventricular Function, Left Ventricular Remodeling β-adrenergic receptor |
| title | Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart |
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