Hypertension activates vessel wall oxygen and metabolism sensing pathways and accelerates atherosclerosis / 中华老年医学杂志

ABSTRACT

Objective To study the molecular mechanism of atherosclerosis induced by intravascular pressure.Methods Technic aortic coarctation (TAC) was performed in ApoE-/-mice (n＝8) and control littermate (n＝8) mice.HE staining was performed in the vessels upstream and downstream of the mice models.In vitro,hypoxia inducible factor-1a (HIF-1α),heme oxygenase,reactive oxygen species and phosphorylated AMP activated protein kinase (AMPK) were analyzed in different intravascular pressure with a myograph system that allowed independent variation of flow and pressure.Results After one month of TAC,ApoE/ mice in a normal chow diet developed occlusive plaque and accelerated atherosclerotic lesions exclusively in upstream high-pressure vessel segments.In vitro,HIF-1α was increased,heme oxygenase was higher over(2.7 ±0.6) fold,reactive oxygen species and phosphorylated AMPK were also enhanced in high intravascular pressure perfused vessel segments as compared with low intravascular pressure perfused vessel segments (all P＜0.05).Conclusions Intravascular pressure elevation can activate hypoxia and metabolism-associated pathways in the arterial wall,and predispose atherosclerosis accelerated.