Paper Title
THERAPEUTIC EFFECTS OF THE DRUG CANDIDATE BGP-15 IN A RAT MODEL OF MONOCROTALINE-INDUCED PULMONARY ARTERIAL HYPERTENSION

Abstract
Introduction: Right-sided heart failure frequently arises due to pulmonary arterial hypertension (PAH), a condition marked by pulmonary vascular abnormalities. This pathological progression is accompanied by an increase in the pulmonary vascular resistance, resulting in the depletion of the compensatory mechanisms within the right ventricle. These impairments eventually lead to irreversible damage of the cardiovascular system and premature mortality.The principal objective of the investigation was to detect the potential therapeutic effects of the BGP-15 in a rat model of monocrotaline-induced pulmonary arterial hypertension. Materials and methods: 12-week-old male Sprague Dawley rats were used. At the beginning of the study PAH was induced by subcutaneous monocrotaline (MCT)injection (60 mg/kg). The experimental animals were randomly divided into 3 groups (n = 15 in each): (1) Control group, received only vehicle; (2) rats that received only MCT leading to PAH development (PAH group); (3) and MCT-injected rats that were treated with 100 mg/kg per os BGP-15 daily, for 8 weeks. At the end of the study echocardiographic measurements were carried out, followed by molecular biological methods. Results: The outcomes of the cardiac ultrasound showed that the rats from the PAH group suffered from diastolic dysfunction. Bothhe LA/Ao and the E/e’ ratios were significantly elevated due to the MCT administration. Moreover, the E/A ratio and the early diastolic myocardial velocity (e’, detected by TDI) were markedly decreased. The BGP-15 treatment improved the diastolic performance, characterized by decreased LA/Ao, E/e’ ratios and increased e’ and E/A ratio. In the PAH model, the shortening of the pulmonary artery acceleration time (PAAT) and the midsystolic notch were observed. In the BGP-15-treated MCT group these impairments were attenuated. The results of the molecular biological techniques indicate that the BGP-15 treatment significantly restored the molecular abnormalities of the PAH model. Conclusions: Although further investigations are needed, our results suggest that the drug candidate BGP-15 may have benefits in the treatment of the pulmonary arterial hypertension. Supported by: TKP2021-EGA-18, ÚNKP-23-3-II-DE-250