The Effect Of YAP-JNK Cascade In The Association Of Atherosclerosis And Hypertension And The Relationship Between Intracranial Atherosclerotic Plaque Formation And Vascular Remodeling

First Part The effect of YAP-JNK signaling pathway in the association of atherosclerosis and high blood pressureBackground and Purpose:Hypertension is an independent risk factor for the atherosclerosis formation,however,the mechanism is unclear.Disturbed blood flow involved in the atherosclerosis formation via up-regulating YAP/JNK signaling pathway.It is known that hypertension can change hemodynamics and induce mechanical disturbances.The study explored the role of YAP/JNK signaling pathway in the formation of atherosclerosis caused by hypertension.Methods:In vivo,male Apo E-deficient on a C57BL/6 background mice(aged 4-6weeks)were treated by 2 g/L N~ω-nitro-L-arginine methyl Ester and fet with west diets or normal diet for eight weeks,for establishing the model of hypertension,hyperlipidemia-induced atherosclerosis and hypertension combined with hyperlipidemia-induced atherosclerosis.Systolic blood pressure was measured every2 week over the course of the study.The aorta and carotid artery were examined to the plaque formation by Oil Red O staining.YAP/JNK expression was determined by western blot in common carotid artery,carotid bifurcation,aortic arch,thoracic aorta.Pro-inflammatory(IL-6、IL-8、SELE)and YAP target genes(CTGF、CYR6I)were further examined by quantitative real-time PCR.In vitro,human umbilical vein endothelial cells are cultured in environments exposed to laminar or disturbed flow combined pressured at 0 h,1 h and 2 h.YAP/JNK expression was examined in these groups by western blot.Results:Atherosclerotic plaques were detected in bifurcation of carotid artery and aortic arch underwent hypertension.The expressions of YAP and p-JNK were increased in common carotid artery,carotid bifurcation,aortic arch,thoracic aorta underwent hypertension,especially in carotid bifurcation and aortic arch.Compared with non-hyper-pressure treated cells,the expressions of YAP and p-JNK were obviously increased in hyper-pressure treated cells.The expressions of IL-6,IL-8,SELE,CTGF and CYR6I genes were significantly higher under hypertension in carotid bifurcation and aortic arch(P<0.05).Conclusion:These data demonstrated that hypertension may promote the atherosclerosis progression via the induction of upregulation of YAP/JNK signaling pathway.Second Part The relationship between intracranial atherosclerotic plaque formation and vascular remodelingBackground and Purpose: Atherosclerotic plaque formation has an effect on the arterial wall,when plaque formed,vascular remodeling occurred in extracranial arteries such as coronary arteries and carotid arteries.This study aims to investigate the relationship between intracranial atherosclerotic plaque and vascular remodeling.Methods: This is a singer-enter retrospective study enrolling 47 patients with acute ischemic cerebrovascular events caused by intracranial large artery atherosclerosis from March 2017 to October 2017.All patients underwent intracranial magnetic resonance imaging,magnetic resonance angiography,and high-resolution magnetic resonance imaging examination within 7 days of symptom onset.Vesselmass software was used to measure the lumen area and outer wall area at the lesion and reference sites,and then the remodeling ratio and plaque burden were calculated.Vascular remodeling is defined as positive remodeling if remodeling ratio > 1.05,intermediate remodeling if 0.95 ≤ remodeling ratio ≤ 1.05,and negative remodeling if remodeling ratio < 0.95.The vascular remodeling of the middle cerebral artery and basilar artery where plaques formed were analyzed and compared.All plaques were divided into 2groups: culprit plaques and non-culprit plaques according to clinical symptoms and imaging examinations.The plaque burden between two groups was compared.Results: There were 72 intracranial plaques in 47 patients,including 47 culprit plaques(65.28%),25 non-culprit plaques(34.72%).There were 51 plaques in the middle cerebral artery and 21(29.17%)in the basilar artery.Compared the middle cerebral artery and basilar artery,the former had a higher proportion to exhibit negative remodeling(47.06% vs.19.05%,P =0.027)and the latter had a higher proportion to exhibit positive remodeling(57.14% vs.25.49%,P =0.010).In addition,the plaque burden of culprit plaques was greater than non-culprit plaques(0.70 ± 0.08 vs.0.65 ± 0.07,P = 0.017).Conclusions: 1.The intracranial arteries exhibit different vascular remodeling when plaques formed.2.The plaques with larger plaque burden are prone to unstable.