| Beta1 integrins modulate beta-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling. | |
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MedLine Citation:
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PMID: 17283249 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sympathetic nerve activity increases in the heart during cardiac failure. Here, we hypothesized that beta1 integrins play a protective role in chronic beta-adrenergic receptor-stimulated cardiac myocyte apoptosis and heart failure. L-isoproterenol (iso; 400 microg/kg per hour) was infused in a group of wild-type (WT) and beta1 integrin heterozygous knockout (hKO) mice. Left ventricular structural and functional remodeling was studied at 7 and 28 days of iso-infusion. Western blot analysis demonstrated reduced beta1 integrin levels in the myocardium of hKO-sham. Iso-infusion increased heart weight:body weight ratios in both groups. However, the increase was significantly higher in WT-iso. M-mode echocardiography indicated increased left ventricular end-diastolic diameter, percentage of fractional shortening, and ejection fraction in the WT-iso group. The percentage of fractional shortening and ejection fraction were significantly lower in hKO-iso versus hKO-sham and WT-iso. Peak left ventricular developed pressure and left ventricular end-diastolic pressure measured using Langendorff-perfusion analyses were significantly higher in the WT-iso group (P<0.05 versus WT-sham and hKO-Iso). The number of TUNEL-positive myocytes was significantly higher in hKO-iso hearts 7 and 28 days after iso-infusion. The increase in myocyte cross-sectional area and fibrosis was higher in the WT-iso group. Matrix metalloproteinase-9 protein levels were significantly higher in WT-iso, whereas matrix metalloproteinase-2 levels were increased in hKO-iso hearts. Iso-infusion increased phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 in both groups. The increase in c-Jun N-terminal kinase phosphorylation was significantly higher in hKO-iso (P<0.001 versus WT-iso). Thus, beta1 integrins play a crucial role in beta-adrenergic receptor-stimulated myocardial remodeling with effects on cardiac myocyte hypertrophy, apoptosis, and left ventricular function. |
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Authors:
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Prasanna Krishnamurthy; Venkateswaran Subramanian; Mahipal Singh; Krishna Singh |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2007-02-05 |
Journal Detail:
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Title: Hypertension Volume: 49 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-03-22 Completed Date: 2007-04-05 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 865-72 Citation Subset: IM |
Affiliation:
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Department of Physiology, James H. Quillen College of Medicine, James H. Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, 37614, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Agonists
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pharmacology* Animals Antigens, CD29 / genetics, metabolism* Apoptosis* Cardiac Output, Low / enzymology, physiopathology*, ultrasonography Echocardiography Extracellular Signal-Regulated MAP Kinases / metabolism Fibrosis Isoproterenol / pharmacology* JNK Mitogen-Activated Protein Kinases / metabolism Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / metabolism Mice Mice, Knockout Myocardial Contraction / drug effects Myocytes, Cardiac* / drug effects, enzymology Phosphorylation / drug effects Pressure Stroke Volume / drug effects Ventricular Function, Left Ventricular Remodeling* |
| Grant Support | |
ID/Acronym/Agency:
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HL-071519/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Antigens, CD29; 7683-59-2/Isoproterenol; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
| Comments/Corrections | |
Comment In:
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Hypertension. 2007 Apr;49(4):767-8
[PMID:
17296873
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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