A study on the role and mechanism of calcium-sensing receptor in pulmonary venous remodeling in pulmonary hypertension mice
GAO Xiaohua
XUE Yan
MO Qiudi
YUAN Hong
PENG Gongyong
Abstract：Objective To study the role and mechanism of calcium-sensing receptor(CaSR)in pulmonary venous remodeling in pulmonary hypertension(PH)mice.Methods A total of 28 C57/BL6 mice were randomly divided into normoxia(Nor)group,normoxia+NPS2143(Nor+NPS)group,hypoxia combined with SU5416(HySu)group and hypoxia combined with SU5416+NPS2143(HySu+NPS)group,with 7 mice in each group.A PH mouse model was developed by feeding under hypoxic(10％O2)condition and injecting SU5416 subcutaneously.PH was assessed by using hemodynamic measurement and right ventricular hypertrophy index(RVHI)analysis,and vascular remodeling was assessed by using Weigert's elastin staining,hematoxylin and eosin(HE)staining,alpha-smooth muscle actin(α-SMA)immunohistochemical staining,and CaSR immunohistochemical staining.The expression levels of CaSR,canonical transient receptor potential protein(TRPC)6 and TRPC4 in pulmonary vein were detected by Western blot.Results The PH mouse model was successfully developed by hypoxia combined with SU5416.The right ventricular systolic pressure(RVSP)and RVHI of mice in the HySu group were significantly higher than those in the Nor group.The distal pulmonary veins of PH mice underwent vascular remodeling,while the proximal pulmonary veins of PH mice showed no vascular remodeling.The expression levels of CaSR and TRPC6 in the PH mice were significantly up-regulated compared with those in the mice of the Nor group(P＜0.05),but there was no significant difference in TRPC4 expression between the PH mice and the mice of the Nor group(P＞0.05).After the intervention with NPS2143,the RVSP and RVHI of mice in the HySu+NPS group were significantly lower than those in the HySu group(P＜0.05),and NPS2143 could significantly alleviate the distal pulmonary venous remodeling induced by hypoxia combined with SU5416,and down-regulated the expressions of CaSR and TRPC6 in the distal pulmonary veins of PH mice(P＜0.05).Conclusion CaSR plays a core role in the remodeling of distal pulmonary veins in PH mice.Hypoxia combined with SU5416 may lead to the upregulation of TRPC6 expression by upregulating the expression of CaSR in the smooth muscle of distal pulmonary veins,leading to the pulmonary venous remodeling.
Keywords：Calcium-sensing receptor(CaSR)Canonical transient receptor potential protein(TRPC)Pulmonary hypertension(PH)Pulmonary venous remodeling
Publication Date：2025-01-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 6-11 )