Abstract 18817: Dysregulation of Key Calcium Cycling Genes Does Not Drive Right Heart Maladaptation in a Porcine PH Model

• Published in: Circulation (New York, N.Y.) N.Y.), 2023-11, Vol.148 (Suppl_1)
• Main Authors: Ravichandran, Anjali J, Mazurek, Renata, Mavropoulos, Spyros, Sakata, Tomoki, Ishikawa, Kiyotake, Marx, Jonas
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.148.suppl_1.18817

Abstract only Introduction: Pulmonary hypertension (PH), a complex disease characterized by an elevated pulmonary artery pressure, causes maladaptation in patients. Maladaptation, or the hemodynamic and functional changes involved in RV/PA uncoupling, leads to poorer outcomes in patients. Dysregulation of calcium cycling controlled by SERCA2a and modulators, PLN and SUMO1, has been shown to cause left heart failure (HF), however its role in right heart maladaptation is unclear. Hypothesis: The dysregulation of the key calcium cycling genes, SERCA2a, PLN, and SUMO1 contributes to the maladaptation in PH. Methods: In this retrospective study, tissues of a porcine Yorkshire model of post-capillary PH were analyzed to understand molecular differences in right ventricular (RV) remodeling resulting in refractory symptom presentation (maladaptive group, n =6) or symptom absence (adaptive group, n =5). Pulmonary and cardiac hemodynamics, functional assessment, echocardiography, and pressure-volume relationship data were collected. Sham control group, ( n =5) received left thoracotomy only. Results: Calcium cycling genes known to be dysregulated in left HF did not display significant differences in group or spatial expression across RV, septal, and LV tissues (Figure). Other significant findings include increases in RV hypertrophy (p