The Expression Of CRT And Caspase-12in The Vascular Smooth Muscle Cellsof The Hypertensive Ratsandtheinterventionaleffectsof1acidipine

Background and objectiveHypertension is one of the most common cardiovascular disease and a majorpublic health problem all over the world. The pathogenesis of hypertension isextremely complex which can be divided into both genetic and environmentalaspects, but the exact mechanism is still unclear. Endoplasmic reticulum stress asthe common pathway of mitochondrial stress and nuclear stress in cellsstimulated the early stage of reaction. Unfolded protein response caused byaggregation of errors and unfolded protein in the endoplasmic reticulum canenhance the function of the endoplasmic reticulum to maintain the balance ofhomeostasis in endoplasmic reticulum via upregulating the expresion ofendoplasmic reticulum molecular chaperone such as calreticulin,glucose-regulated protein78,94, etc. However, when the unfolded proteinexceeds the processing capacity of the endoplasmic reticulum can lead toapoptosis. Existing studies had confirmed that endoplasmic reticulum stressplayed an important role in the development of heart failure and ischemiccardiomyopathy, but the mechanisms of ERS in vascular smooth muscle in hypertension was not clear. Lacidipine is a novel third-generation dihydropyridiecalcium channel blocker. Studies had shown that lacidipine could effectivelylower blood pressure and could reduce the damage of target organs such asheart,brain and kidney, but the molecular mechanism of lacidipine to protect thetarget organs is still unclear. In this study, we made hypertensive rats byabdominal aortic stenosis surgery to observe the expression of protection andinjury factors of ERS and the changes of MAP, and to detect the expression ofCRT and caspase-12intervention by lacidipine. We aimed to further study themolecular mechanisms of ERS in VSMCS and to explore the role of ERS inprogress that lacidipine lower blood pressure.MethodsHypertensive rats were used as experiment models by abdominal aorticstenosis surgery in this study. We used experimental techniques and methodssuch as western-blot, immuno-histochemistry and so on to detect the MAP, theexpression of CRT and caspase-12, media thickness of artery and the impact oflacidipine on the factors of ERS.Results(1) Mean arterial blood pressure (MAP) of the model group increasedprogressively during the experiment, and the4w and8w subgroups were higherthan those in corresponding control groups (P<0.01).(2) Compared with controlgroups，the artery media thickness of the subgroups of4w、8w in the model groupincreased significantly (P<0.05).(3) The expression of CRT in the subgroups of1w、4w、8w (their optical density were0.183±0.013,0.389±0.017,0.424±0.021)in the model group increased significantly (P<0.05) compared with control group（their optical density were0.106±0.008,0.144±0.010,0.137±0.011）.(4) Theexpression of caspase-12in the subgroups of1w、4w、8w (their optical densitywere0.174±0.012,0.405±0.019,0.437±0.023) in the model group increased significantly (P<0.05) compared with control group（their optical density were0.118±0.007,0.123±0.008,0.131±0.009）.(5) The apoptosis rate of vascularsmooth muscle cells in the subgroup of8w in the model group were higher thanthose in corresponding control group and1w、4w subgroups of modelgroup(P<0.05).(6) the mean arterial blood pressure of abdominal transverse aorticconstriction group (TAC group)is higher than the control group and lacidipinegroup(P<0.05).(7) Compared with control group and lacidipine group, theartery media thickness of TAC group increased significantly (P<0.05).(8)Theexpression of CRT and caspase-12in vascular smooth muscle cells of TAC groupwas higher than it in control group (RCRT/β-actin:0.102±0.006and0.417±0.015，Rcasepase-12/β-actin0.196±0.009and0.482±0.019，p<0.01); The expression of CRTand caspase-12in vascular smooth muscle cells of TAC group was higher than itin lacidipine group （RCRT/β-actin:0.204±0.01and0.417±0.015，Rcasepase-12/β-actin:0.219±0.012与0.482±0.019,p<0.01）.(9) Compared with controlgroup and lacidipine group, the apoptosis rate of vascular smooth muscle cells ofTAC group was significant higher(P<0.01).ConclusionHigh blood pressure results from abdominal aortic stenosis can causeendoplasmic reticulum stress response of vascular smooth muscle cell. Lacidipinemay exerts an protective effect on vascular smooth muscle cell by inhibiting theendoplasmic reticulum stress via down-regulating the expression of CRT andcaspase-12.