Document Detail


Adiponectin deficiency, diastolic dysfunction, and diastolic heart failure.
MedLine Citation:
PMID:  19850745     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aldosterone infusion results in left ventricular hypertrophy (LVH) and hypertension and may involve profibrotic and proinflammatory mechanisms. In turn, hypertension is the major cause of diastolic heart failure (HF). Adiponectin, an adipose-derived plasma protein, exerts antiinflammatory and anti-hypertrophic effects and is implicated in the development of hypertension and systolic HF. We thus tested the hypothesis that hypoadiponectinemia in aldosterone-induced hypertension exacerbated cardiac remodeling and diastolic HF. Wild-type (WT) or adiponectin-deficient (APNKO) mice underwent saline or aldosterone infusion and uninephrectomy and were fed 1% salt water for 4 wk. Blood pressure was increased in aldosterone-infused WT (132 +/- 2 vs. 109 +/- 3 mm Hg; P < 0.01) and further augmented in APNKO mice (140 +/- 3 mm Hg; P < 0.05 vs. aldosterone-infused WT). LVH was increased in aldosterone-infused WT vs. WT mice (LV/body weight ratio, 4.8 +/- 0.2 vs. 4.1 +/- 0.2 mg/g) and further increased in aldosterone-infused APNKO mice (LV/body weight ratio, 6.0 +/- 0.4 mg/g). Left ventricular ejection fraction was not decreased in either aldosterone-infused WT or APNKO hearts. Pulmonary congestion however was worse in APNKO mice (P < 0.01). The ratio of early ventricular filling over late ventricular filling (E/A) and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e'), measures of diastolic function, were increased in aldosterone-infused WT hearts and further increased in APNKO hearts (P < 0.05 for both). Renal function and cardiac fibrosis were no different between both aldosterone-infused groups. Aldosterone increased matrix metalloproteinase-2 expression in WT hearts (P < 0.05 vs. WT and P < 0.01 vs. APNKO). Myocardial atrial natriuretic peptide, interferon-gamma, and TNF-alpha expression were increased in aldosterone-infused WT hearts. Expression of these proteins was further increased in aldosterone-infused APNKO hearts. Therefore, hypoadiponectinemia in hypertension-induced diastolic HF exacerbates LVH, diastolic dysfunction, and diastolic HF. Whether or not adiponectin replacement prevents the progression to diastolic HF will warrant further study.
Authors:
Flora Sam; Toni-Ann S Duhaney; Kaori Sato; Richard M Wilson; Koji Ohashi; Saki Sono-Romanelli; Akiko Higuchi; Deepa S De Silva; Fuzhong Qin; Kenneth Walsh; Noriyuki Ouchi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-22
Journal Detail:
Title:  Endocrinology     Volume:  151     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-23     Completed Date:  2010-02-22     Revised Date:  2011-07-19    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  322-31     Citation Subset:  AIM; IM    
Affiliation:
Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA. flora.sam@bmc.org
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MeSH Terms
Descriptor/Qualifier:
Adiponectin / blood,  genetics,  metabolism,  physiology
Animals
Biological Markers / analysis,  blood
Blood Pressure / genetics,  physiology
Diastole / genetics*,  physiology
Echocardiography, Doppler
Fibrosis
Heart / anatomy & histology,  physiopathology
Heart Failure, Diastolic / blood,  genetics*,  physiopathology
Hypertension / blood,  complications,  genetics,  physiopathology
Hypertrophy, Left Ventricular / genetics,  metabolism,  physiopathology
Kidney / physiology
Matrix Metalloproteinases / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium / metabolism,  pathology
Tissue Inhibitor of Metalloproteinases / metabolism
Grant Support
ID/Acronym/Agency:
HL079099/HL/NHLBI NIH HHS; R21 HL095891-02/HL/NHLBI NIH HHS; R37 AG015052-15/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Adiponectin; 0/Biological Markers; 0/Tissue Inhibitor of Metalloproteinases; 0/adiponectin, mouse; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections

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