Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: Heart failure causes severe lung disease

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

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1170-1178
Number of pages9
JournalHypertension
Volume59
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Pulmonary hypertension
  • Pulmonary vascular morphology
  • Transverse aortic constriction

ASJC Scopus subject areas

  • Internal Medicine

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