1. The Preventive Effect And Potential Mechanism Of XAV939 On Pulmonary Arterial Hypertension In Rats 2. Increased Risk Of Hypertension In Young Adults In Southwest China: Impact Of The 2017 ACC/AHA High Blood Pressure Guideline

Background and Objective pulmonary arterial hypertension(PAH)is considered as a pulmonary vascular proliferative disease with cancer-like properties,which has many potential cancer pathogenic mechanisms.Currently,therapeutic drugs of PAH are mainly used to improve vasoconstriction/vasodilation abnormalities.Therefore,exploring drugs that inhibit the abnormal proliferation of pulmonary vascular cells and ameliorate pulmonary vascular remodeling has become a research hotspot.XAV939 is a small molecule compound with anti-tumor effect,which plays an important role in inhibiting the proliferation,migration and invasion of various tumor cells.Whether it can be applied to the treatment of PAH has not been studied.This study aims to investigate the effects of XAV939 on monocrotaline(MCT)-induced PAH in rats and its possible mechanism,to provide experiment and theory for clinical treatment of PAH.Methods art 1 Effects and mechanism of XAV939 on MCT-induced PAH inrats. xty healthy male SD(Spragye-Dawley)rats were randomly assigned into the following groups: control group,XAV939 group,MCT group and MCT+ XAV939 group,with 15 rats in each group.The mean pulmonary artery pressure(mPAP)and right ventricular systolic pressure(RVSP)were measured by right heart catheterization(RHC).Systemic blood pressure(SBP)was measured by left common carotid artery catheterization.Cardiac function was evaluated by echocardiography.The effect of XAV939 on MCT-induced PAH was observed.Taking the lung tissue of each groups.Hematoxylin eosin(HE)staining to observe the histological changes.Immunohistochemistry assay was used to detect the expression of alpha smooth muscle actin(?-SMA).Western blot was used to detect the expression levels of the key proteins of involved in the Wnt/?-catenin signaling pathways such as: ?-catenin,GSK-3?,p-GSK-3? and Cyclin D1.Part 2 Effect and mechanism of XAV939 on Platelet-derived Growth Factor(PDGF)-induced pulmonary artery smooth muscle cells(PASMCs)proliferation and migration. Primary rat PASMCs were isolated,cultured and identified.Divided into four groups: control group,XAV939 group,PDGF group and PDGF +XAV939 group.The proliferation,migration and cell cycle of PASMCs were detected by CCK-8,scratch test and flow cytometry,respectively.Western blot was used to detect the expression levels of the key proteins of Wnt/?-catenin signaling pathways such as: ?-catenin,GSK-3?,p-GSK-3?and Cyclin D1.Results In vivo,XAV939 significantly reduced mPAP,RVSP and right ventricular transection diameter(RVTD),and increased tricuspid annulus plane systolic excursion(TAPSE)and ejection fraction(EF)in MCT-induced PAH rats,effectively attenuating the development of PAH.HE staining showed that XAV939 significantly inhibited pulmonary vascular remodeling in MCT-induced PAH rats,and the results of ?-SMA immunohistochemistry further showed that XAV939 significantly inhibited MCT-induced pulmonary artery smooth muscle layer thickening in MCT-induced PAH rats.In addition,XAV939 down-regulated the expression levels of ?-catenin and Cyclin D1 proteins,and up-regulated the expression levels of GSK-3? and p-GSK-3? proteins in lung tissues of MCT-induced PAH rats.In vitro,XAV939 pretreatment significantly inhibited PDGF-induced abnormal proliferation and migration of PASMCs,inhibited the up-regulation of ?-catenin and Cyclin D1,and down-regulation of GSK-3? and p-GSK-3? by PDGF.Conclusion XAV939 can ameliorate pulmonary artery remodeling and right ventricular function in MCT-induced PAH rats,thereby attenuating thedevelopment of PAH.The mechanism may be that XAV939 can inhibit the activation of Wnt/?-catenin signaling pathway,and inhibiting the abnormal proliferation and migration of PASMCs.Purpose To examine the impact of the new 2017 ACC/AHA Hypertension Guideline on the prevalence of hypertension,its constituent ratio,and their associated factors in Southwest China.Recent Findings A total of 14220 permanent residents ? 18 years were enrolled in this survey.According to the 2017 ACC/AHA Hypertension Guideline,the hypertension prevalence was substantially increased(46.9% vs.24.5%),consistent across different age and gender groups,while the hypertension awareness(23.8% vs.45.6%),treatment(18.6% vs.35.5%),control(2.3%vs.11.2%),and control among treatment(9.6% vs.24.0%)patients were decreased in southwest of China.In our cohort,31.1% participants were newly diagnosed as hypertension.Young adults accounted considerable proportion in this newly diagnosed hypertension population.The proportion of young hypertensive individuals substantially increased,whereas those of the older hypertensive subjects decreased.Among the ypertensive subjects aged ?65 years undergoing treatment,90% of the elderly subjects were not eligible for hypertension control and 32.5% have systolic blood pressure control at 130–149 mm Hg and thus need to intensify antihypertensive treatment according to 2017 ACC/AHA Hypertension Guideline.Smoking,drinking,body fat percentage,and body mass index were considered the factors associated with hypertension according to the Chinese Hypertension Guideline but not in the 2017ACC/AHA Hypertension Guideline.Summary The adoption of the 2017 ACC/AHA Hypertension Guideline will substantially increase hypertension prevalence in southwest of China.The new definition of hypertension implies that more young adults will likely suffer from high cardiovascular risks,while additional one-third of elder hypertensive subjects will likely need intensified antihypertension treatments.