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Left Ventricular Failure Produces Profound Lung Remodeling and Pulmonary Hypertension in Mice: Heart Failure Causes Severe Lung Disease

Hypertension (Dallas, Tex. 1979), 2012-06, Vol.59 (6), p.1170-1178 [Peer Reviewed Journal]

2012 American Heart Association, Inc. ;2015 INIST-CNRS ;ISSN: 0194-911X ;EISSN: 1524-4563 ;DOI: 10.1161/HYPERTENSIONAHA.111.186072 ;PMID: 22508832 ;CODEN: HPRTDN

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Title:
Left Ventricular Failure Produces Profound Lung Remodeling and Pulmonary Hypertension in Mice: Heart Failure Causes Severe Lung Disease
Author: Chen, Yingjie ; Guo, Haipeng ; Xu, Dachun ; Xu, Xin ; Wang, Huan ; Hu, Xinli ; Lu, Zhongbing ; Kwak, Dongmin ; Xu, Yawei ; Gunther, Roland ; Huo, Yuqing ; Weir, E Kenneth
Subjects: Animals ; Aorta - pathology ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Blotting, Western ; Cardiology. Vascular system ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Collagen - genetics ; Collagen - metabolism ; Constriction, Pathologic - complications ; Fibrosis - etiology ; Heart Failure - complications ; Heart Failure - metabolism ; Heart Failure - physiopathology ; Hypertension, Pulmonary - etiology ; Hypertension, Pulmonary - metabolism ; Hypertension, Pulmonary - physiopathology ; Hypertrophy, Left Ventricular - complications ; Hypertrophy, Left Ventricular - metabolism ; Hypertrophy, Left Ventricular - physiopathology ; Hypoxia - physiopathology ; Leukocytes - metabolism ; Leukocytes - pathology ; Lung - metabolism ; Lung - pathology ; Lung - physiopathology ; Lung Diseases - etiology ; Lung Diseases - metabolism ; Lung Diseases - physiopathology ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Organ Size ; Pulmonary Edema - etiology ; Pulmonary Edema - metabolism ; Pulmonary Edema - physiopathology ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - metabolism ; Ventricular Dysfunction, Left - complications ; Ventricular Dysfunction, Left - metabolism ; Ventricular Dysfunction, Left - physiopathology ; Water - metabolism
Is Part Of: Hypertension (Dallas, Tex. 1979), 2012-06, Vol.59 (6), p.1170-1178
Description: 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.
Publisher: Hagerstown, MD: American Heart Association, Inc
Language: English
Identifier: ISSN: 0194-911X
EISSN: 1524-4563
DOI: 10.1161/HYPERTENSIONAHA.111.186072
PMID: 22508832
CODEN: HPRTDN
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE

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Left Ventricular Failure Produces Profound Lung Remodeling and Pulmonary Hypertension in Mice: Heart Failure Causes Severe Lung Disease

2012 American Heart Association, Inc. ;2015 INIST-CNRS ;ISSN: 0194-911X ;EISSN: 1524-4563 ;DOI: 10.1161/HYPERTENSIONAHA.111.186072 ;PMID: 22508832 ;CODEN: HPRTDN

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