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Which have observed a comparable degree of `RV resilience' inside the setting of stress and volume overload [31]. We next examined the effect of RVPO on ventricular mass and initially observed that total physique weight was substantially decreased in main RVPO, not secondary RVPO. In spite of this profound difference in total body weight, RV mass enhanced to the very same degree in both models of RVPO even though LV mass was lowered in principal RVPO, but improved in secondary RVPO. Modifications in cardiomyocyte cross-sectional location have been consistent with alterations in ventricular mass. Importantly, seven days of LV pressure overloadBiventricular RemodelingFigure 3. Hypertrophic remodeling in models of primary and secondary correct ventricular stress overload (RVPO). A) Representative histologic staining of suitable 24195657 24195657 (RV) and left (LV) ventricular tissue and B) bar graph of RV and LV cardiomyocyte cross-sectional areas after main and secondary RVPO. C) Western blot and D) bar graph of RV and LV calcineurin protein expression normalized to GAPDH. E) Calcineurin-Ab (CN-PP), F) brain natriuretic peptide (BNP), G) beta-myosin heavy chain (b-MHC), and H) sarcoplasmic reticulum Ca2+ATPase (SERCa) gene expression normalized to total ribosomal RNA (rRNA). *, p,0.05 vs Sham for the corresponding ventricle; {, p,0.05 vs Primary RVPO for the corresponding ventricle; `, p,0.05 vs the RV for the same RVPO condition. doi:10.1371/journal.pone.0070802.gincreased LV mass, but did not affect RV mass, thereby suggesting that RV remodeling is a later consequence of LV pressure overload. A recent clinically study reported a similar pattern ofatrophic remodeling of the LV in pulmonary hypertension that may be reversible in conditions such as chronic thromboembolic pulmonary hypertension [32]. One possible explanation forBiventricular RemodelingFigure 4. Fibrotic remodeling in models of primary and secondary right ventricular pressure overload (RVPO). A) Picrosirius red staining for collagen abundance and B) quantitation of percent fibrosis in the right (RV) and left ventricle (LV) after primary and secondary RVPO. C) Western blot and D) bar graph of Type I collagen normalized to GAPDH. E ) Gene expression of transforming growth factor beta 1 (TGFb1) and endoglin normalized to ribosomal RNA (rRNA). G ) Quantified protein expression of phosphorylated ERK (pERK) normalized to total ERK and phosphorylated Smad-3 normalized to total Smad-3. *, p,0.05 vs Sham for the corresponding ventricle; {, p,0.05 vs Primary RVPO for the corresponding ventricle; `, p,0.05 vs the RV for the same RVPO condition. doi:10.1371/journal.pone.0070802.g`atrophic remodeling of the LV in primary RVPO is the reduction in LV stroke work that occurs with reduced LV preload due to fixed pulmonary vascular obstruction. Future studies are needed to define the cause and BI-D1870 significance of LV remodeling in RVPO. Ourfindings now extend this clinical observation to a preclinical model and further show no significant change in LV contractile function despite reduced LV mass in primary RVPO.Biventricular RemodelingNext, we explored two central pathways that mediate cardiac remodeling, namely, signaling via calcineurin 23977191 23977191 and TGFb1. Based on numerous studies of left heart failure, calcineurin has been identified as regulator of cardiac hypertrophy, fetal gene expression, and fibrosis [22?4]. Few studies have examined calcineurin expression in models of right heart failure [25]. We now show that both primary and secondary RVPO are associated wi.