| Hypertensive patients with elevated serum homocysteine (homocysteine, Hcy)concentration are called "H-type" hypertension. China has about150million people sufferfrom "H-type" hypertension, and its incidence is much higher than abroad. Highhomocysteine (Hyperhomocysteine, HHcy) and hypertension have synergistic manner,HHcy aggravated hypertension on target organ damage. Recent clinical studies haveshown that the level of the development of left ventricular hypertrophy with serum Hcyhas a close relationship. But there is not yet definitive evidence that HHcy withhypertension and left ventricular hypertrophy have a direct relationship. Pathogenicpathways of HHcy is complex, multiple molecular mechanisms, including endothelialdysfunction, vascular smooth muscle cell proliferation, platelet aggregation, insulinresistance, procoagulant and anticoagulant mechanism imbalances may be involved in thedevelopment of related cardiovascular and cerebrovascular diseases. However, studies onthe molecular mechanism of HHcy effect on left ventricular hypertrophy are short.Previous studies within our group demonstrated endoplasmic reticulum stress(endoplasmic reticulum stress, ERS) are one of the molecular mechanisms of hypertension-induced left ventricular hypertrophy. A variety of reasons cause smallperipheral arteries, high blood pressure, cardiac pressure overload, triggering myocardialERS, ERS protection factor GRP78, GRP94and other pro-apoptotic factorsstress-CHOP, caspase12expression imbalance, such as persistent severe stress resulting inthe expression of pro-apoptotic factors predominate, mediated apoptosis in cardiacmyocyte hypertrophy, left ventricular hypertrophy on clinical eventually appear. WhetherERS is HHcy left ventricular hypertrophy on the role of one of the molecular mechanismshave not been reported.Enalapril folic acid tablets are second-generation angiotensin converting enzymeinhibitor formulated with folic acid to10mg/0.8mg new composite formulations clinicallyfor the treatment of essential hypertension in patients with HHcy. Enalapril mainlyproduce the antihypertensive effect by inhibiting the RAS system, folic acid can promoteHcy methylation process, reduce serum Hcy. Studies have shown that folic acid tabletsenalapril not only lower blood pressure and serum Hcy levels, but also reduce theincidence of cardiovascular-related adverse events. However, the effect of the interventionand the intervention mechanisms of hypertension and left ventricular hypertrophy withHHcy are unclear. Based on the above conditions, the experiment will use the abdominalaortic coarctation and high methionine diet for hypertension and HHcy rats, and folic acidtablets using enalapril treatment intervention. By using a series of testing methods anddetection indicators to examine whether HHcy can aggravate hypertension left ventricularhypertrophy, and ERS is one of the molecular mechanisms of its pathogenic; enalaprilfolic acid tablets can improve with hypertension with HHcy and left ventricularhypertrophy and explore its molecular mechanism. Through this study, in order to providea new theoretical basis and prevention strategies for the "H-type" high blood pressureLVH, reducing "H-type" dangers of high blood pressure.Methods:In this study, operation of abdominal aortic coarctation for hypertensive rats modelpreparation, two weeks later choose systolic pressure (SBP)±140mmHg hypertensive ratsfor the study. These hypertensive rats were randomly divided into three groups, control group, high methionine group (HM) and Enalapril folic acid (EFA) group, each group wasdivided into subgroups of four weeks and eight weeks. Rat tail artery noninvasive bloodpressure measurement and analysis system of rats was used to measured SBP; Hcydetector test serum Hcy concentration; weighed rat body mass, heart mass and leftventricular mass, calculated left ventricular mass/body mass and left heart mass/heartmass; HE staining of pathological changes in myocardial tissue; immunohistochemistryand Western blot to detect changes in myocardial cells expression of GRP78and CHOP.Results：①4weeks, the HM group SBP were slightly higher than controls, but the differencesbetween the two groups was not significant (P>0.05); compared with the HM group, SBPof the EFA group was significantly lower (P <0.05). At8weeks, the HM group SBP wassignificantly higher than controls (P <0.05); compared with the HM group, the EFA groupSBP were significantly lower (P <0.01).②With the growth of feeding time, serum Hcyconcentrations were significantly increased in HM group, but serum Hcy concentration ofthe control group no significant increase, compared with the controls, serum Hcyconcentration of the HM group was significantly increase (P<0.01); compared with theHM group four weeks, eight weeks subgroups, the serum Hcy concentration of EFA groupcorresponding subgroups was significantly decreased (P <0.01).③the HWI and LVWI ofcontrol group and the HM group were significantly increased at4weeks,8weekssubgroups, and the HM group increased more significantly (P<0.05); the HWI and LVWIof EFA group corresponding sub-groups were significantly lower(P<0.05), comparedwith HM group4weeks,8week subgroup.④the control and the HM group myocardialcells GRP78expression had a increasing reduction with the growth of stress time; fourweeks, rats’ cardiomyocytes of eight weeks subgroups of the HM GRP78expression werehigher than the control group corresponding subgroup (P <0.05); rat cardiomyocytes offour weeks, eight weeks subgroups of the EFA group GRP78expression was significantlylower than the HM group corresponding subgroup (P <0.05);⑤CHOP expressions of thecontrol group and HM group myocardial cells increased by the growth of stress time; theHM group four weeks, rat cardiomyocytes CHOP expression of eight weeks subgroups were significantly higher than the control group corresponding subgroup (P <0.05), ratcardiomyocytes CHOP expressions of the EFA group four weeks, eight weeks subgroupswere significantly lower than the HM group corresponding subgroup (P <0.05)Conclusion：Cardiac pressure overload triggers rat myocardial cells ERS, and high serum Hcyconcentrations that aggravates myocardial cells ERS, leads to the imbalanced expressionof ERS-related factors GRP78and CHOP, promotes the dominant expression of apoptoticfactor CHOP, ultimately causes left ventricular hypertrophy aggravated; EnalaprilPlymouth folic acid tablets effectively reduce blood pressure and serum Hcy concentrationand release myocardial ERS, reduce the expression of GRP78and CHOP, therebyprotecting cardiac cells, effectively reversing left ventricular hypertrophy. So we thinkHHcy aggravates hypertension and left ventricular hypertrophy, ERS may be one of thepathogenic mechanisms of molecular biology; Enalapril Folic Acid tablets may inhibit theendoplasmic reticulum stress to protect myocardial cells, improve left ventricularhypertrophy. |
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