Document Detail


Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease.
MedLine Citation:
PMID:  22508832     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic left ventricular failure causes pulmonary congestion with increased lung weight and type 2 pulmonary hypertension. Understanding the molecular mechanisms for type 2 pulmonary hypertension and the development of novel treatments for this condition requires a robust experimental animal model and a good understanding of the nature of the resultant pulmonary remodeling. Here we demonstrate that chronic transverse aortic constriction causes massive pulmonary fibrosis and remodeling, as well as type 2 pulmonary hypertension, in mice. Thus, aortic constriction-induced left ventricular dysfunction and increased left ventricular end-diastolic pressure are associated with a ≤5.3-fold increase in lung wet weight and dry weight, pulmonary hypertension, and right ventricular hypertrophy. Interestingly, the aortic constriction-induced increase in lung weight was not associated with pulmonary edema but resulted from profound pulmonary remodeling with a dramatic increase in the percentage of fully muscularized lung vessels, marked vascular and lung fibrosis, myofibroblast proliferation, and leukocyte infiltration. The aortic constriction-induced left ventricular dysfunction was also associated with right ventricular hypertrophy, increased right ventricular end-diastolic pressure, and right atrial hypertrophy. The massive lung fibrosis, leukocyte infiltration, and pulmonary hypertension in mice after transverse aortic constriction clearly indicate that congestive heart failure also causes severe lung disease. The lung fibrosis and leukocyte infiltration may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. Thus, the effective treatment of left ventricular failure may require additional efforts to reduce lung fibrosis and the inflammatory response.
Authors:
Yingjie Chen; Haipeng Guo; Dachun Xu; Xin Xu; Huan Wang; Xinli Hu; Zhongbing Lu; Dongmin Kwak; Yawei Xu; Roland Gunther; Yuqing Huo; E Kenneth Weir
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-04-16
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-17     Completed Date:  2012-07-25     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1170-8     Citation Subset:  IM    
Affiliation:
Lillehei Heart Institute and the Cardiovascular Division, University of Minnesota Medical School, Minneapolis, MN 55455, USA. chenx106@umn.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / physiopathology
Aorta / pathology
Blotting, Western
Collagen / genetics,  metabolism
Constriction, Pathologic / complications
Fibrosis / etiology
Heart Failure / complications,  metabolism,  physiopathology
Hypertension, Pulmonary / etiology,  metabolism,  physiopathology*
Hypertrophy, Left Ventricular / complications,  metabolism,  physiopathology*
Leukocytes / metabolism,  pathology
Lung / metabolism,  pathology,  physiopathology*
Lung Diseases / etiology,  metabolism,  physiopathology
Male
Mice
Mice, Inbred C57BL
Organ Size
Pulmonary Edema / etiology,  metabolism,  physiopathology
Reverse Transcriptase Polymerase Chain Reaction
Transforming Growth Factor beta / genetics,  metabolism
Ventricular Dysfunction, Left / complications,  metabolism,  physiopathology*
Water / metabolism
Grant Support
ID/Acronym/Agency:
1R01 HL079168/HL/NHLBI NIH HHS; R01 HL105406/HL/NHLBI NIH HHS; R01HL105406/HL/NHLBI NIH HHS; R01HL65322/HL/NHLBI NIH HHS; R21 HL098669/HL/NHLBI NIH HHS; R21 HL098719/HL/NHLBI NIH HHS; R21 HL102597/HL/NHLBI NIH HHS; R21HL098669/HL/NHLBI NIH HHS; R21HL098719/HL/NHLBI NIH HHS; R21HL102597/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Transforming Growth Factor beta; 7732-18-5/Water; 9007-34-5/Collagen
Comments/Corrections

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