CXCR4 ANTAGONIST AMD3100 PROMOTES MILD IMPROVEMENTS OF CARDIAC FUNCTION AND PULMONARY MECHANICS IN PULMONARY HYPERTENSIVE RATS

Abstract

Background Pulmonary arterial hypertension (PAH) is a lethal cardiopulmonary disease characterized by an increase in resting pulmonary pressure ≥25 mmHg. Poor survival and functional limitations of PAH patients have fueled research for new alternative therapeutic strategies. So far, pre-clinical findings suggested promising effects of stem cell-based therapies. AMD3100 is a highly selective CXCR4 antagonist that enhances autologous bone marrow-derived stem cell mobilization and is currently used in stem cell transplantation and the treatment of leukemia. So far, however, it remains unclear whether AMD3100 can provide salutary effects in the treatment of PAH. Methods PAH was induced in adult male Wistar rats (Protocol number 087/15) by an intraperitoneal injection of monocrotaline (MCT, 60 mg/kg IP), while the Control (CTL) group was treated an equivalent volume of vehicle. Two weeks after the MCT injection, MCT-administered rats were randomly treated with AMD3100 (1 mg/kg/day IP for 14 days) or vehicle, totalling 3 groups: CTL, MCT, and AMD3100. Echocardiography and pneumotachography were used to assess cardiac function and pulmonary mechanics, respectively. Right ventricular (RV) hypertrophy was assessed by the Fulton index. Data were analyzed with One-way and Two-way ANOVA (Prism®, GraphPad) and were expressed as mean ± SEM. Results MCT and AMD3100 groups exhibited an equally progressive decrease in body weight compared to the CTL group (p Conclusion Our study indicates that treatment with AMD3100 provides mild improvement of cardiac and pulmonary function in pulmonary hypertensive rats.