Pls3突变相关新型早发骨质疏松大鼠模型的心血管改变及机制OA北大核心CSTPCD

Objective To evaluate the cardiovascular phenotype and its relationship to collagen metabolism in a novel rat model of early-onset osteoporosis(EOOP)induced by Pls3 mutation.Methods Comparison of cardiac pheno-type was completed between rats with knockout of the 10-16 exons of Pls3(Pls3E10-16del/0)constructed by CRISPR/Cas9 technology and wild type rats.Immunohistochemical staining was used to evaluate the expression of PLS3 in cardiovascular tissues.Echocardiography was used to assess cardiovascular morphology and function.H&E staining was used to evaluate the histological change of myocardial tissue.The collagen microstructure and arrangement were evaluated by scanning elec-tron microscopy.Results In the cytoplasm of the cardiovascular tissues,PLS3 was widely expressed in wild-type rats,and significantly decreased in Pls3E10-16del/0 rats.At 6-8 weeks of age,no significant structural and functional abnormalities were observed in the heart and great vessels of Pls3E10-16del/0 rats.However,compared with wild-type rats,Pls3E10-16del/0 rats showed reductions in right ventricular end-diastolic diameter and proximal ascending aorta diameter.In Pls3E10-16del/0 rats,collagen synthesis in cardiovascular tissues was not affected,but electron microscopy showed that fine collagen fibers were broken and disorganized in the heart and ascending aorta.Conclusion We firstly evaluated the cardiovascular phenotype of a new Pls3E10-16del/0 rat model with EOOP,which had decreased internal diameter of the right ventricle and ascending aorta,broken and scattered fine collagen fibers.The effects of mutation in Pls3 on the cardiovascular system need to be observed for a long time.This study expands the understanding of the cardiovascular phenotype of rare Pls3-associated ear-ly-onset osteoporosis.