Linked Life Data

20800067

Source:http://linkedlifedata.com/resource/pubmed/id/20800067

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-12
pubmed:abstractText
Despite significant advances in pharmacological and clinical treatment, heart failure (HF) remains a leading cause of morbidity and mortality worldwide. HF is a chronic and progressive clinical syndrome characterized by a reduction in left ventricular (LV) ejection fraction and adverse remodeling of the myocardium. The past several years have seen remarkable progress using animal models in unraveling the cellular and molecular mechanisms underlying HF pathogenesis and progression. These studies have revealed potentially novel therapeutic targets/strategies. The application of cardiac gene transfer, which allows for the manipulation of targets in cardiomyocytes, appears to be a promising therapeutic tool in HF. ?-adrenergic receptor (?AR) dysfunction represents a hallmark abnormality of chronic HF, and increased G protein-coupled receptor kinase 2 (GRK2) levels/activity in failing myocardium is among these alterations. In the past 15years, several animal studies have shown that expression of a peptide inhibitor of GRK2 (?ARKct) can improve the contractile function of failing myocardium including promoting reverse remodeling of the LV. Therefore, data support the use of the ?ARKct as a promising candidate for therapeutic application in human HF. Importantly, recent studies in cardiac-specific GRK2 knockout mice have corroborated GRK2 being pathological in failing myocytes. The purpose of this review is to discuss: 1) the alterations of ?AR signaling that occur in HF, 2) the evidence from transgenic mouse studies investigating the impact of GRK2 manipulation in failing myocardium, 3) the therapeutic efficacy of in vivo ?ARKct gene therapy in HF, and 4) the intriguing possibility of lowering HF-related sympathetic nervous system hyperactivity by inhibiting GRK2 activity in the adrenal gland. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy".
pubmed:grant
http://linkedlifedata.com/resource/pubmed/grant/P01 HL075443-040002, http://linkedlifedata.com/resource/pubmed/grant/P01 HL075443-050002, http://linkedlifedata.com/resource/pubmed/grant/P01 HL091799-02, http://linkedlifedata.com/resource/pubmed/grant/P01 HL091799-03, http://linkedlifedata.com/resource/pubmed/grant/R01 HL056205-10, http://linkedlifedata.com/resource/pubmed/grant/R01 HL056205-11, http://linkedlifedata.com/resource/pubmed/grant/R01 HL056205-12, http://linkedlifedata.com/resource/pubmed/grant/R01 HL061690-10, http://linkedlifedata.com/resource/pubmed/grant/R01 HL061690-11, http://linkedlifedata.com/resource/pubmed/grant/R01 HL085503-01A1, http://linkedlifedata.com/resource/pubmed/grant/R01 HL085503-02, http://linkedlifedata.com/resource/pubmed/grant/R01 HL085503-03, http://linkedlifedata.com/resource/pubmed/grant/R01 HL085503-04, http://linkedlifedata.com/resource/pubmed/grant/R37 HL061690-12, http://linkedlifedata.com/resource/pubmed/grant/R37 HL061690-13
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1095-8584
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
785-92
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
GRK2 as a novel gene therapy target in heart failure.
pubmed:affiliation
Center for Translational Medicine and George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
pubmed:publicationType
Journal Article, Review