Comparing calcium handling in right and left ventricle cardiomyocytes in type III pulmonary hypertension
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Type III pulmonary hypertension (PH) is characterized by pulmonary fibrosis, leading to elevated pressure in the pulmonary arteries and hypertrophy of the right ventricle (RV). Yet, effects of PH on cardiomyocyte calcium handling are unclear. This study addresses the hypothesis that RV cardiomyocytes will show altered excitation-contraction coupling (ECC) as compared to left ventricle (LV) cardiomyocytes in a mouse PH model. To assess this, male C57BL/6 mice were treated with intratracheal saline (sham) or bleomycin (Bleo;0.025 units) to induce type III PH. On days 21-24 post-treatment, animals were anesthetized, hearts were excised, and perfused for enzymatic cell isolation. Isolated RV and LV cardiomyocytes were loaded with fluo-5F for calcium measurements during ECC. Calcium transient amplitude was measured at 0.5 Hz, and sarcoplasmic reticulum (SR) calcium content was determined by rapid application of 10 mM caffeine. Bleo-treated mouse hearts showed RV hypertrophy, indicating PH development and RV remodeling. Calcium transient amplitude and reuptake kinetics reveal ECC alterations and impaired SR Calcium ATPase (SERCA) activity in RV cardiomyocytes of the PH model. Interestingly, SR calcium content was not different between Bleo and sham groups in either RV or LV cardiomyocytes. Thus, this study emphasizes mechanisms underlying RV versus LV dysfunction in type III PH, indicating therapeutic interventions targeting cardiomyocyte calcium handling may improve outcomes in patients with PH.
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M.S.