Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure
Background Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circ...
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| Veröffentlicht in: | European journal of preventive cardiology 2014-01, Vol.21 (1), p.4-11 |
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| creator | Rengo, Giuseppe Galasso, Gennaro Femminella, Grazia D Parisi, Valentina Zincarelli, Carmela Pagano, Gennaro Lucia, Claudio De Cannavo, Alessandro Liccardo, Daniela Marciano, Caterina Vigorito, Carlo Giallauria, Francesco Ferrara, Nicola Furgi, Giuseppe Filardi, Pasquale Perrone Koch, Walter J Leosco, Dario |
| description | Background
Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients.
Methods
For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months.
Results
Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p |
| doi_str_mv | 10.1177/2047487313491656 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1469219176</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_2047487313491656</sage_id><sourcerecordid>1469219176</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-3d3a88767f5188cbb8a60cb2cffb41582930e91e8d97c18d87a2ac0d4669484c3</originalsourceid><addsrcrecordid>eNp1kUFrFTEQxxdRbKm9e5JchHpYTbLZZHKUok-xIBQ9L9nspC91X7Im2er7DH5pU96zguBcZhh-8x_mP03znNHXjCn1hlOhBKiOdUIz2ctHzel9qxUA7PFDrbqT5jznW1pDUs4BnjYnvJOge96fNr-ucVpt8TGQ6Mi83y3baPcFyYYsKRb0obVxXWacSEKLS4mJfPPBZGw5udhcf-KviHEFE8GfmKzPSEoyPvhwUwVw8rZkktd05-_MTHwgiykeQ23-8GVLtmhSIc74eU34rHnizJzx_JjPmq_v3325_NBefd58vHx71VpBdWm7qTMASirXMwA7jmAktSO3zo2C9cB1R1EzhEkry2ACZbixdBJSagHCdmfNxUG3Xvh9xVyGnc8W59kEjGsemJCaM82UrCg9oDbFnBO6YUl-Z9J-YHS4_8Lw7xfqyIuj-jrucHoY-ON5BV4eAZOtmV0yofr2lwMmKDBaufbAZXODw21cU6iu_H_xb2fUnSQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1469219176</pqid></control><display><type>article</type><title>Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>SAGE Complete</source><source>Alma/SFX Local Collection</source><creator>Rengo, Giuseppe ; Galasso, Gennaro ; Femminella, Grazia D ; Parisi, Valentina ; Zincarelli, Carmela ; Pagano, Gennaro ; Lucia, Claudio De ; Cannavo, Alessandro ; Liccardo, Daniela ; Marciano, Caterina ; Vigorito, Carlo ; Giallauria, Francesco ; Ferrara, Nicola ; Furgi, Giuseppe ; Filardi, Pasquale Perrone ; Koch, Walter J ; Leosco, Dario</creator><creatorcontrib>Rengo, Giuseppe ; Galasso, Gennaro ; Femminella, Grazia D ; Parisi, Valentina ; Zincarelli, Carmela ; Pagano, Gennaro ; Lucia, Claudio De ; Cannavo, Alessandro ; Liccardo, Daniela ; Marciano, Caterina ; Vigorito, Carlo ; Giallauria, Francesco ; Ferrara, Nicola ; Furgi, Giuseppe ; Filardi, Pasquale Perrone ; Koch, Walter J ; Leosco, Dario</creatorcontrib><description>Background
Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients.
Methods
For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months.
Results
Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome.
Conclusions
Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.</description><identifier>ISSN: 2047-4873</identifier><identifier>EISSN: 2047-4881</identifier><identifier>DOI: 10.1177/2047487313491656</identifier><identifier>PMID: 23689525</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Aged ; Biological and medical sciences ; Biomarkers - blood ; Cardiology. Vascular system ; Down-Regulation ; Exercise Therapy ; Female ; G-Protein-Coupled Receptor Kinase 2 - metabolism ; Heart ; Heart Failure - blood ; Heart Failure - diagnosis ; Heart Failure - enzymology ; Heart Failure - mortality ; Heart Failure - physiopathology ; Heart Failure - therapy ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Humans ; Italy ; Kaplan-Meier Estimate ; Lymphocytes - enzymology ; Male ; Medical sciences ; Middle Aged ; Natriuretic Peptide, Brain - blood ; Norepinephrine - blood ; Oxygen Consumption ; Peptide Fragments - blood ; Proportional Hazards Models ; Prospective Studies ; Stroke Volume ; Time Factors ; Treatment Outcome ; Ventricular Function, Left</subject><ispartof>European journal of preventive cardiology, 2014-01, Vol.21 (1), p.4-11</ispartof><rights>The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-3d3a88767f5188cbb8a60cb2cffb41582930e91e8d97c18d87a2ac0d4669484c3</citedby><cites>FETCH-LOGICAL-c409t-3d3a88767f5188cbb8a60cb2cffb41582930e91e8d97c18d87a2ac0d4669484c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/2047487313491656$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/2047487313491656$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,4010,21798,27900,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28140810$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23689525$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rengo, Giuseppe</creatorcontrib><creatorcontrib>Galasso, Gennaro</creatorcontrib><creatorcontrib>Femminella, Grazia D</creatorcontrib><creatorcontrib>Parisi, Valentina</creatorcontrib><creatorcontrib>Zincarelli, Carmela</creatorcontrib><creatorcontrib>Pagano, Gennaro</creatorcontrib><creatorcontrib>Lucia, Claudio De</creatorcontrib><creatorcontrib>Cannavo, Alessandro</creatorcontrib><creatorcontrib>Liccardo, Daniela</creatorcontrib><creatorcontrib>Marciano, Caterina</creatorcontrib><creatorcontrib>Vigorito, Carlo</creatorcontrib><creatorcontrib>Giallauria, Francesco</creatorcontrib><creatorcontrib>Ferrara, Nicola</creatorcontrib><creatorcontrib>Furgi, Giuseppe</creatorcontrib><creatorcontrib>Filardi, Pasquale Perrone</creatorcontrib><creatorcontrib>Koch, Walter J</creatorcontrib><creatorcontrib>Leosco, Dario</creatorcontrib><title>Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure</title><title>European journal of preventive cardiology</title><addtitle>Eur J Cardiovasc Prev Rehabil</addtitle><description>Background
Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients.
Methods
For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months.
Results
Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome.
Conclusions
Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.</description><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Cardiology. Vascular system</subject><subject>Down-Regulation</subject><subject>Exercise Therapy</subject><subject>Female</subject><subject>G-Protein-Coupled Receptor Kinase 2 - metabolism</subject><subject>Heart</subject><subject>Heart Failure - blood</subject><subject>Heart Failure - diagnosis</subject><subject>Heart Failure - enzymology</subject><subject>Heart Failure - mortality</subject><subject>Heart Failure - physiopathology</subject><subject>Heart Failure - therapy</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Humans</subject><subject>Italy</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphocytes - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Natriuretic Peptide, Brain - blood</subject><subject>Norepinephrine - blood</subject><subject>Oxygen Consumption</subject><subject>Peptide Fragments - blood</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Stroke Volume</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Ventricular Function, Left</subject><issn>2047-4873</issn><issn>2047-4881</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUFrFTEQxxdRbKm9e5JchHpYTbLZZHKUok-xIBQ9L9nspC91X7Im2er7DH5pU96zguBcZhh-8x_mP03znNHXjCn1hlOhBKiOdUIz2ctHzel9qxUA7PFDrbqT5jznW1pDUs4BnjYnvJOge96fNr-ucVpt8TGQ6Mi83y3baPcFyYYsKRb0obVxXWacSEKLS4mJfPPBZGw5udhcf-KviHEFE8GfmKzPSEoyPvhwUwVw8rZkktd05-_MTHwgiykeQ23-8GVLtmhSIc74eU34rHnizJzx_JjPmq_v3325_NBefd58vHx71VpBdWm7qTMASirXMwA7jmAktSO3zo2C9cB1R1EzhEkry2ACZbixdBJSagHCdmfNxUG3Xvh9xVyGnc8W59kEjGsemJCaM82UrCg9oDbFnBO6YUl-Z9J-YHS4_8Lw7xfqyIuj-jrucHoY-ON5BV4eAZOtmV0yofr2lwMmKDBaufbAZXODw21cU6iu_H_xb2fUnSQ</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>Rengo, Giuseppe</creator><creator>Galasso, Gennaro</creator><creator>Femminella, Grazia D</creator><creator>Parisi, Valentina</creator><creator>Zincarelli, Carmela</creator><creator>Pagano, Gennaro</creator><creator>Lucia, Claudio De</creator><creator>Cannavo, Alessandro</creator><creator>Liccardo, Daniela</creator><creator>Marciano, Caterina</creator><creator>Vigorito, Carlo</creator><creator>Giallauria, Francesco</creator><creator>Ferrara, Nicola</creator><creator>Furgi, Giuseppe</creator><creator>Filardi, Pasquale Perrone</creator><creator>Koch, Walter J</creator><creator>Leosco, Dario</creator><general>SAGE Publications</general><general>Sage Publications</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>201401</creationdate><title>Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure</title><author>Rengo, Giuseppe ; Galasso, Gennaro ; Femminella, Grazia D ; Parisi, Valentina ; Zincarelli, Carmela ; Pagano, Gennaro ; Lucia, Claudio De ; Cannavo, Alessandro ; Liccardo, Daniela ; Marciano, Caterina ; Vigorito, Carlo ; Giallauria, Francesco ; Ferrara, Nicola ; Furgi, Giuseppe ; Filardi, Pasquale Perrone ; Koch, Walter J ; Leosco, Dario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-3d3a88767f5188cbb8a60cb2cffb41582930e91e8d97c18d87a2ac0d4669484c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Cardiology. Vascular system</topic><topic>Down-Regulation</topic><topic>Exercise Therapy</topic><topic>Female</topic><topic>G-Protein-Coupled Receptor Kinase 2 - metabolism</topic><topic>Heart</topic><topic>Heart Failure - blood</topic><topic>Heart Failure - diagnosis</topic><topic>Heart Failure - enzymology</topic><topic>Heart Failure - mortality</topic><topic>Heart Failure - physiopathology</topic><topic>Heart Failure - therapy</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Humans</topic><topic>Italy</topic><topic>Kaplan-Meier Estimate</topic><topic>Lymphocytes - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Natriuretic Peptide, Brain - blood</topic><topic>Norepinephrine - blood</topic><topic>Oxygen Consumption</topic><topic>Peptide Fragments - blood</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Stroke Volume</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Ventricular Function, Left</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rengo, Giuseppe</creatorcontrib><creatorcontrib>Galasso, Gennaro</creatorcontrib><creatorcontrib>Femminella, Grazia D</creatorcontrib><creatorcontrib>Parisi, Valentina</creatorcontrib><creatorcontrib>Zincarelli, Carmela</creatorcontrib><creatorcontrib>Pagano, Gennaro</creatorcontrib><creatorcontrib>Lucia, Claudio De</creatorcontrib><creatorcontrib>Cannavo, Alessandro</creatorcontrib><creatorcontrib>Liccardo, Daniela</creatorcontrib><creatorcontrib>Marciano, Caterina</creatorcontrib><creatorcontrib>Vigorito, Carlo</creatorcontrib><creatorcontrib>Giallauria, Francesco</creatorcontrib><creatorcontrib>Ferrara, Nicola</creatorcontrib><creatorcontrib>Furgi, Giuseppe</creatorcontrib><creatorcontrib>Filardi, Pasquale Perrone</creatorcontrib><creatorcontrib>Koch, Walter J</creatorcontrib><creatorcontrib>Leosco, Dario</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>European journal of preventive cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rengo, Giuseppe</au><au>Galasso, Gennaro</au><au>Femminella, Grazia D</au><au>Parisi, Valentina</au><au>Zincarelli, Carmela</au><au>Pagano, Gennaro</au><au>Lucia, Claudio De</au><au>Cannavo, Alessandro</au><au>Liccardo, Daniela</au><au>Marciano, Caterina</au><au>Vigorito, Carlo</au><au>Giallauria, Francesco</au><au>Ferrara, Nicola</au><au>Furgi, Giuseppe</au><au>Filardi, Pasquale Perrone</au><au>Koch, Walter J</au><au>Leosco, Dario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure</atitle><jtitle>European journal of preventive cardiology</jtitle><addtitle>Eur J Cardiovasc Prev Rehabil</addtitle><date>2014-01</date><risdate>2014</risdate><volume>21</volume><issue>1</issue><spage>4</spage><epage>11</epage><pages>4-11</pages><issn>2047-4873</issn><eissn>2047-4881</eissn><abstract>Background
Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients.
Methods
For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months.
Results
Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome.
Conclusions
Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>23689525</pmid><doi>10.1177/2047487313491656</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Biological and medical sciences Biomarkers - blood Cardiology. Vascular system Down-Regulation Exercise Therapy Female G-Protein-Coupled Receptor Kinase 2 - metabolism Heart Heart Failure - blood Heart Failure - diagnosis Heart Failure - enzymology Heart Failure - mortality Heart Failure - physiopathology Heart Failure - therapy Heart failure, cardiogenic pulmonary edema, cardiac enlargement Humans Italy Kaplan-Meier Estimate Lymphocytes - enzymology Male Medical sciences Middle Aged Natriuretic Peptide, Brain - blood Norepinephrine - blood Oxygen Consumption Peptide Fragments - blood Proportional Hazards Models Prospective Studies Stroke Volume Time Factors Treatment Outcome Ventricular Function, Left |
| title | Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure |
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