ACE2 improves right ventricular function in a pressure overload model.

Johnson JA, West J, Maynard KB, Hemnes AR
PLoS One. 2011 6 (6): e20828

PMID: 21695173 · PMCID: PMC3112229 · DOI:10.1371/journal.pone.0020828

BACKGROUND - Right ventricular (RV) dysfunction is a complication of pulmonary hypertension and portends a poor prognosis. Pharmacological therapies targeting RV function in pulmonary hypertension may reduce symptoms, improve hemodynamics, and potentially increase survival. We hypothesize that recombinant human angiotensin-converting enzyme 2 (rhACE2) will improve RV function in a pressure overload model.

RESULTS - rhACE2 administered at 1.8 mg/kg/day improved RV systolic and diastolic function in pulmonary artery banded mice as measured by in vivo hemodynamics. Specifically, rhACE2 increased RV ejection fraction and decreased RV end diastolic pressure and diastolic time constant (p<0.05). In addition, rhACE2 decreased RV hypertrophy as measured by RV/LV+S ratio (p<0.05). There were no significant negative effects of rhACE2 administration on LV function. rhACE2 had no significant effect on fibrosis as measured by trichrome staining and collagen1α1 expression. In pulmonary artery banded mice, rhACE2 increased Mas receptor expression and normalized connexin 37 expression.

CONCLUSION - In a mouse RV load-stress model of early heart failure, rhACE2 diminished RV hypertrophy and improved RV systolic and diastolic function in association with a marker of intercellular communication. rhACE2 may be a novel treatment for RV failure.

MeSH Terms (18)

Animals Diastole Disease Models, Animal Fibrosis Hemodynamics Humans Hypertrophy, Right Ventricular Immunohistochemistry Male Mice Mice, Inbred C57BL Microvessels Peptidyl-Dipeptidase A Pressure Recombinant Proteins Signal Transduction Systole Ventricular Function, Right

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