The mechanism of bone morphogenetic protein 2 regulating pulmonary vascular remodeling in pulmonary hypertension
10.3760/cma.j.cn115455-20221208-01086
- VernacularTitle:骨形成蛋白2调节肺动脉高压肺血管重构的作用机制研究
- Author:
Jingyi MAI
1
;
Xiaolin RAO
;
Yong CAI
;
Shunna LIN
Author Information
1. 广州市第十二人民医院儿科，广州 510620
- Keywords:
Pulmonary hypertension;
Vascular remodeling;
Bone morphogenetic protein 2;
Cell proliferation;
Apoptosis
- From:
Chinese Journal of Postgraduates of Medicine
2023;46(8):763-768
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of bone morphogenetic protein 2 (BMP-2) regulating pulmonary vascular remodeling in pulmonary hypertension (PH).Methods:Pulmonary artery smooth muscle cells (PASMC) groups: control group, PH group, PH+BMP-2 group, PH+BMP-2+ small interfering BMP receptor(si-BMPR)-Ⅰa group, PH+BMP-2+ si-BMPR-Ⅰb group, PH+BMP -2+si-BMPR-Ⅱ group. In vitro PH model was induced by hypoxia. The three BMP-2 receptors were silenced by the transfection of si-BMPR-Ⅰa, si-BMPR-Ⅰb and si-BMPR-Ⅱ plasmids, respectively. Cell proliferation and apoptosis in each group were detected, transient receptor potential ion channel C1/6 (TRPC1/6), p21 mRNA and protein levels, and intracellular Ca 2+ concentration were detected. Results:The intracellular Ca 2+ concentration in the PH group was higher than that in the control group: (785.15 ± 44.26) nmol/L vs. (224.15 ± 15.87) nmol/L, the and apoptosis rate was lower than that in the control group: (3.15 ± 0.22)% vs. (7.31 ± 0.45)%, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP-2 group was (297.64 ± 21.46) nmol/L, and was lower than that in the PH group, and apoptosis rate was (6.88 ± 0.75)%, and was higher than that in the PH group, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP-2+si-BMPR-Ⅰa group, PH+BMP-2+ si-BMPR-Ⅰb group, PH+BMP -2+si-BMPR-Ⅱ group was (412.31 ± 29.57), (384.34 ± 30.66), (695.23 ± 39.85) nmol/L, and was higher than that in the PH+BMP-2 group, and apoptosis rate was (4.10 ± 0.27)%, (4.26 ± 0.28)%, (3.33 ± 0.24)%, and was lower than that in the PH+BMP-2 group, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP -2+si-BMPR-Ⅱ group was higher than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+ si-BMPR-Ⅰb group, the apoptosis rate was lower than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+ si-BMPR-Ⅰb group, there were statistical differences ( P<0.05). Conclusions:BMP-2 mainly inhibits the expression of TRPC1/6 by interacting with the receptor BMPR-Ⅱ, inhibits the influx of Ca 2+ and promotes the expression of p21, thereby inhibiting the proliferation of PASMC and promoting apoptosis, participating in pulmonary vascular remodeling in PH.
