186 Effects of an established drug on smad signalling pathway in the rat model of monocrotaline pulmonary hypertension. (4th June 2021)

• Record Type: Journal Article
• Authors: Habas, Khaled; Eklioğlu, Özlem; Nasim, Talat
• Is Part Of: Heart. Volume 107(2021)Supplement 1
• Page Start: A144
• Page End: A145
• Publication Date: 2021-06-04
• Subjects: Pulmonary arterial hypertension -- SMADs -- BMPRII; Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-2021-BCS.183
• Languages: English
• ISSNs: 1355-6037

Abstract

Abstract : Introduction: Pulmonary arterial hypertension (PAH) is a complex multifactorial disease with both genetic and environmental dynamics contributing to disease progression that characterized by unbalanced proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) (Nasim et al., 2012). Mutations in the bone morphogenetic protein receptor type II (BMPRII) gene have been associated with development of familial pulmonary artery hypertension (PAH). The function of SMAD signal transduction during the pulmonary vasculature and the role BMPRII mutations in the development of PAH are not fully understood. However, drug or toxin-induced PAH has been characterized by raised pulmonary arterial resistance leading to right heart failure. Aim and Methods: in this study, the monocrotaline (MCT) model of PAH was used to examine alterations in SMADs (SMAD3 and SMAD1/5) signal transduction pathways in vivo. The SMAD signalling pathways were investigated in lungs harvested from rats treated with a single 50-mg/kg of MCT and an established drug at concentrations of 0.5 and 1 mg/Kg. The level of phosphorylation of SMAD3 and SMAD1/5 were detected by Western blot and the expression BMPR2, Id1, Pai1 transcripts was measured using quantitative real time PCR (qPCR). Results: MCT-treated rats decreased the level of SMAD 3 phosphorylation, which was restored following the treatment with the established drug. The drug also modulated the expression of SMAD target genes. Conclusion: Our study suggests that loss of SMAD3 could possibly present a key event in the pathophysiology in PAH and restoring this pathway may provide therapeutic intervention. Conflict of Interest: The authors declare that there is no conflict of interest