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Right ventricular dysfunction and pulmonary hypertension are common in HFpEF, and thought to be driven by obesity and metabolic syndrome. Thus, we hypothesized that an animal model of obesity\u2010induced HFpEF with pulmonary hypertension would provide insight into the pathogenesis of right ventricular failure in HFpEF. Two strains of mice, one susceptible (AKR) and one resistant (C3H) to obesity\u2010induced HFpEF, were fed high fat (60% fat) or control diet for 0, 2, or 20 weeks and evaluated by cardiac catheterization and echocardiography for development of right ventricular dysfunction, pulmonary hypertension, and HFpEF. AKR, but not C3H, mice developed right ventricular dysfunction, pulmonary hypertension, and HFpEF. <jats:italic>NPRC<\/jats:italic>, which antagonizes beneficial natriuretic peptide signaling, was found in RNA sequencing to be the most differentially upregulated gene in the right ventricle, but not left ventricle or lung, of AKR mice that developed pulmonary hypertension and HFpEF. Overexpression of <jats:italic>NPRC<\/jats:italic> in H9C2 cells increased basal cell size and increased expression of hypertrophic genes, <jats:italic>MYH7<\/jats:italic> and <jats:italic>NPPA<\/jats:italic>. In conclusion, we have shown that <jats:italic>NPRC<\/jats:italic> contributes to right ventricular modeling in obesity\u2010induced pulmonary hypertension\u2010HFpEF by increasing cardiomyocyte hypertrophy. <jats:italic>NPRC<\/jats:italic> may represent a promising therapeutic target for right ventricular dysfunction in pulmonary hypertension\u2010HFpEF.<\/jats:p>","DOI":"10.1177\/2045894019895452","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T11:25:42Z","timestamp":1574940342000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":29,"title":["Natriuretic peptide receptor C contributes to disproportionate right ventricular hypertrophy in a rodent model of obesity\u2010induced heart failure with preserved ejection fraction with pulmonary 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