Abstract: Objective To investigate the phenotypic and functional differences of endothelial cells derived from induced pluripotent stem cells (iPSC-ECs) between HPAH patient (HPAH) and Control donor (CON), and clarify the molecular mechanism of phenotypic changes in BMPRII deficient ECs which is a pathological characteristic of PAH. Methods Differentiate the iPSCs derived from human pulmonary arterial smooth muscle cells (hPASMCs) to ECs. The expression of several genes related to stem cell and endothelial marker were analyzed at different time points during the differentiation. Immunofluorescence staining showed the expression of surface markers of iPSC-ECs. The transcription factors involved in the EndoMT process were detected by real-time quantitative PCR (qPCR). HPAH and CON-derived iPSC-ECs were compared for tube formation. VEGFR2 mRNA and protein expression were detected by qPCR and immunofluorescence staining. Results The expression of several endothelial cell related genes of HPAH were different from CON during differentiationthrough they both expressed pluripotency genes. The expression of α-SMA, HMGA1, Slug and Snail1 in HPAH iPSC-ECs were significantly higher compared with CON ECs (P<0.05). The tube formation of HPAH-derived ECs reduced which could be rescued by VEGF165. Their VEGFR2 mRNA and protein expression were lower compared with CON ECs. Conclusions It suggests that enhanced HMGA1, Slug and Snail1 genes involve in the EndoMT of iPSC-ECs from HAPH, reduced VEGFR2 may contribute to tube formation dysfunctionin pulmonary vascular remodeling of PAH.

Key words: Key words PAH, endothelial cells, EndoMT, VEGFR2