Linked Life Data

20231526

Source:http://linkedlifedata.com/resource/pubmed/id/20231526

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-4-15
pubmed:abstractText
We cloned a novel molecule interacting with angiotensin II type 1 receptor, which we named ATRAP (for angiotensin II type 1 receptor-associated protein). Previous in vitro studies showed that ATRAP significantly promotes constitutive internalization of the angiotensin II type 1 receptor and further attenuates angiotensin II-mediated hypertrophic responses in cardiomyocytes. The present study was designed to investigate the putative functional role of ATRAP in cardiac hypertrophy by angiotensin II infusion in vivo. We first examined the effect of angiotensin II infusion on endogenous ATRAP expression in the heart of C57BL/6J wild-type mice. The angiotensin II treatment promoted cardiac hypertrophy, concomitant with a significant decrease in cardiac ATRAP expression, but without significant change in cardiac angiotensin II type 1 receptor expression. We hypothesized that a downregulation of the cardiac ATRAP to angiotensin II type 1 receptor ratio is involved in the pathogenesis of cardiac hypertrophy. To examine this hypothesis, we next generated transgenic mice expressing ATRAP specifically in cardiomyocytes under control of the alpha-myosin heavy chain promoter. In cardiac-specific ATRAP transgenic mice, the development of cardiac hypertrophy, activation of p38 mitogen-activated protein kinase, and expression of hypertrophy-related genes in the context of angiotensin II treatment were completely suppressed, in spite of there being no significant difference in blood pressure on radiotelemetry between the transgenic mice and littermate control mice. These results demonstrate that cardiomyocyte-specific overexpression of ATRAP in vivo abolishes the cardiac hypertrophy provoked by chronic angiotensin II infusion, thereby suggesting ATRAP to be a novel therapeutic target in cardiac hypertrophy.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1157-64
pubmed:meshHeading
pubmed-meshheading:20231526-Adaptor Proteins, Signal Transducing, pubmed-meshheading:20231526-Angiotensin II, pubmed-meshheading:20231526-Angiotensin II Type 1 Receptor Blockers, pubmed-meshheading:20231526-Animals, pubmed-meshheading:20231526-Blood Pressure, pubmed-meshheading:20231526-Body Weight, pubmed-meshheading:20231526-Cardiomegaly, pubmed-meshheading:20231526-Genotype, pubmed-meshheading:20231526-Heart Rate, pubmed-meshheading:20231526-Imidazoles, pubmed-meshheading:20231526-Male, pubmed-meshheading:20231526-Mice, pubmed-meshheading:20231526-Mice, Inbred C57BL, pubmed-meshheading:20231526-Mice, Inbred Strains, pubmed-meshheading:20231526-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:20231526-RNA, pubmed-meshheading:20231526-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20231526-Tetrazoles
pubmed:year
2010
pubmed:articleTitle
Cardiac-specific activation of angiotensin II type 1 receptor-associated protein completely suppresses cardiac hypertrophy in chronic angiotensin II-infused mice.
pubmed:affiliation
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't