Apelin‐13 Attenuates Right Ventricular Hypertrophy and Pulmonary Fibrosis in a Monocrotaline Model of Pulmonary Hypertension

Pulmonary hypertension (PH) is a progressive and fatal disease characterised by pulmonary vascular remodelling, right ventricular hypertrophy, and increased pulmonary arterial pressure. Apelin, an endogenous ligand of the APJ receptor, exerts cardioprotective and vasoprotective effects and has been proposed as a potential therapeutic agent in PH. This study aimed to investigate the therapeutic effects of Apelin-13 on hemodynamic, histomorphological, and molecular alterations in a monocrotaline (MCT)-induced PH rat model. Male Wistar rats were divided into four groups: control, MCT, MCT + Apelin-13, and sham-Apelin. A single intraperitoneal injection of MCT (60 mg/kg) was used to induce PH. Apelin-13 was administered intraperitoneally for 21 days. Hemodynamic parameters (P_max, P_min, mPAP, EDP, dP/dt_max, dP/dt_min, MAP), morphometric indices (RVHI, PAWTR, PAVR), histological and immunohistochemical analyses (Apelin-13, ACE, Caspase-3, IL-1β) were evaluated. MCT administration significantly increased pulmonary arterial pressure, right ventricular hypertrophy, and vascular wall thickness, while reducing Apelin-13 and ACE expression and elevating Caspase-3 and IL-1β levels. Apelin-13 treatment markedly attenuated these pathological alterations by lowering right ventricular overload, improving vascular remodelling, restoring Apelin-13 and ACE expression, and reducing apoptotic and inflammatory markers. Apelin-13 exerts multifaceted protective effects in MCT-induced PH by modulating hemodynamic load, vascular structure, and inflammatory-apoptotic pathways. These findings provide novel evidence supporting Apelin-13 as a promising therapeutic candidate for PH and warrant further studies to explore its long-term efficacy and translational potential.