Assessment Of Osteopontin,Osteoprotegerin And Activated Monocytes/Macrophages On Vascular Calcification In Patients With Hypertension

Background and Objectives: Vascular calcification(VC)is an important risk factor of cardiovascular disease.We evaluate the cardiovascular risk factors,organ damage,clinical diseases and arterial stiffness during hypertensive patients with or without VC.Monocytes/macrophages are believed to play a role in VC.Here,we analyzed whether osteopontin(OPN)and osteoprotegrin(OPG)affect inflammatory factors of cultured macrophages from hypertensive patients with/without VC.Methods: 1.In this study,527 hypertensive subjects with or without VC were identified by using artery electronic calculators tomography.2.Human peripheral blood CD14+ monocytes,including CD11c+ and CD163+ cells,were analyzed by flow cytometry.3.OPN,OPG activated macrophages differentiated from peripheral blood mononuclear cells of hypertensive subjects with patients in vitro.The effects on M1 and M2 macrophages correlated with cytokines and chemokines were assessed by real-time qPCR.4.Histological analysis was performed on the samples of aortic blood vessels from calcified vessels and stained by alizarin red or immunohistochemistry.Results: We showed that in hypertensive subjects,VC was correlated with higher systolic pressure,higher incidence and higher intima-media thickness of the carotid artery,higher morbidity of cardiovascular diseases including diabetes mellitus,stroke,and coronary atherosclerosis,and was associated with arterial stiffness including higher carotid-femoral pulse wave velocity,aortic systolic pressure,augment pressure,and augment index(P<0.05).Furthermore,CD14+ and CD14+CD11c+CD163-cells from human peripheral blood were significantly increased in HT patients with VC(P<0.05).VC could promote both pro-inflammatory(M2)and anti-inflammatory(M1)macrophages inflammatory factors.Serum levels of both OPN and OPG were increased in hypertensive subjects with VC.They could not affect macrophages inflammatory factors on hypertensive patients without VC.However,both of them could significantly upregulated anti-inflammatory M2 macrophages inflammatory factors,and OPN could also downregulated pro-inflammatory M1 macrophages inflammatory factors(P<0.05).Moreover,we found the expressions of OPN and OPG were increased in calcific vessel walls.Conclusion: VC aggravates organ damages,cardiovascular diseases and arterial stiffness of hypertensive subjects.The inflammatory factors of both M1 and M2 macrophages are promoted by VC.OPN and OPG could regulate inflammatory factors of macrophages.These data provide novel insight into the link between inflammation and VC diseases.