Atrial and Brain Natriuretic Peptides Expression and Release in Right Heart Failure

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Introduction: Pulmonary arterial hypertension (PAH) is characterized by right ventricular (RV) overload. N-terminal Brain Natriuretic Peptides (NT-proBNP) and Atrial Natriuretic Peptides (ANP) are secreted from cardiomyocytes upon stretch. Aim: To investigate the association between ANP and NTproBNP and pressure overload in blood, right heart tissue and induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) from PAH-patients. Methods: We analyzed NT-proBNP and MR-proANP levels in N=76 PAH-patients and N=18 controls. We measured NPPA and NPPB expression in end-stage human RV and right atrial (RA) tissue from N=8 PAH and N=5 controls and performed immunofluorescence staining for ANP and BNP on RA (N=4) and RV PAH tissue (N=10) and in controls (N=5). iPSC-CMs from PAH-patients were stretched for 24h at 1Hz and 10% on the Flexcell FX-6000 system. NTproBNP and MRproANP release was measured. Differences were assessed using a t-test. Results: NTproBNP and MRproANP levels were elevated in PH vs controls (296[85–675] vs 43[32-71] pg/mL, p<0.001 and 110[76–161] vs 53[44-74] pg/mL, P<0.001 respectively) (Fig1A, B). NPPBA expression was upregulated in PAH RV tissue, but NPPB was not. ANP and BNP content was higher in PAH RA and RV tissue (Fig 1C). NTproBNP and MRproANP was released from iPSC-CMs after mechanical stretch. Conclusions: ANP and BNP showed important differences at gene and protein levels in relation to pressure overload. erj;66/suppl_69/PA6160/F1 F1 F1

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