title: Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease.
abstract: 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.affiliation: Lillehei Heart Institute and the Cardiovascular Division, University of Minnesota Medical School, Minneapolis, MN 55455, USA. chenx106@umn.edu
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Chen
authors.forename: Haipeng
authors.initials: H
authors.lastname: Guo
authors.forename: Dachun
authors.initials: D
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Xinli
authors.initials: X
authors.lastname: Hu
authors.forename: Zhongbing
authors.initials: Z
authors.lastname: Lu
authors.forename: Dongmin
authors.initials: D
authors.lastname: Kwak
authors.forename: Yawei
authors.initials: Y
authors.lastname: Xu
authors.forename: Roland
authors.initials: R
authors.lastname: Gunther
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.forename: E Kenneth
authors.initials: EK
authors.lastname: Weir
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D015153:Blotting, Western; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003251:Constriction, Pathologic / Q000150:complications; D005355:Fibrosis / Q000209:etiology; D006333:Heart Failure / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D014867:Water / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D014867:Water; D003094:Collagen