| Objective:It was found that Pathological myocardial hypertrophy of the left ventricle is the most common complication of hypertension,and it is one of the independent risk factors for increased mortality from cardiovascular disease.Therefore,one of the important goals of the current treatment of hypertension is to reverse myocardial hypertrophy.It is reported that sialylation is upregulated during the occurrence of myocardial hypertrophy.This research focuses on sialyltransferase 7A(Siat7A),which is the only gene that has a continuously increasing expression among the nearly 20,000 genes tested and has nothing to do with genetic background in hypertrophic myocardial tissue of hypertensive rats.Hypoxia-inducible factor 1(Hif-1)is a heterodimer transcription factor composed of Hif-1? and Hif-1?.Among them,Hif-1? is increased in the early stage of pathological ventricular hypertrophy.Although Hif-1a has a short-term beneficial effect on pressure overload or acute ischemia,it has a short duration of action,and chronic long-term increase of Hif-1? has a worsening effect on the heart.Therefore,the objectives of this study are:1.To detect the role of Siat7 A and Hif-1?protein expression in pathological cardiomyocyte hypertrophy.2.To clarify whether or not the expression of hypoxia-inducible factor-1?(Hif-1?)is regulated by Siat7 A in cardiomyocyte hypertrophy.3.To detect whether Hif-1? plays a role in pathological myocardial hypertrophy.Material and Methods:Histopathological sections of clinical patients;Cell AC16;Four lentiviruses infect AC16 cells,and select stably expressed sh Siat7 A,sh Hif-1?,over Siat7 A cell lines;Wistar rat;Evaluation of myocardial hypertrophy with HE staining.Detection of Siat7 A and Hif-1? expression by immunohistochemical staining.The m RNA expression levels of Siat7 A,Hif-1?,ANPand Hif-1? were detected by q-PCR technology.Western Blotting was used to detect the expression levels of Siat7 A,Hif-1? and ANP.Results:Siat7A and Hif-1? increased expression in cardiac tissue of patients with hypertensive myocardial hypertrophy.AC16 cells,cells infected by lentivirus carrying empty plasmids or sh Siat7 A sequence plasmids,cells infected bylentivirus carrying empty plasmids or Siat7 A sequence plasmids,cells infected by lentivirus carrying an empty plasmid or sh Hif-1? sequence plasmid were treated with 0 ?M and 1 ?M Ang? in vitro.The results were as followings:In AC16 cells,the expression of Siat7 A,Hif-1?,ANP protein increased after Ang?(0?M,1?M)treatment for 24 hours.After knocking down Siat7 A gene,Siat7 A protein expression was suppressed,ANP protein expression was reduced,and Hif-1? protein expression was also reduced.After over-expressing Siat7 A,Siat7A protein expression was increased,ANP protein expression was increased,and Hif-1? protein expression was also increased.Knocking down Hif-1? expression reduced ANP expression,But Siat7 A protein expression does not decrease.In AC16 cells,the expression level of Hif-1? m RNA was unchanged after Ang?(24 h,1 ?M)treatment.After knocking down Siat7 A expression,Hif-1? m RNA expression level was also unchanged.Adeno-associated virus(AAV9)carrying sh Siat7 A was injected into the left ventricular wall of rat heart in vivo,and angiotensin ? was continuously injected to induce cardiac hypertrophy in rats.Under the cardiac troponin T(c TNT)promoter,AAT9 vector encoding Siat7 A was specifically transfused into rat,myocardium,and infusion of angiotensin ? induced cardiac hypertrophy in rats.The results show that knockout of Siat7 A down-regulates Hif-1? and alleviates myocardial hypertrophy induced by Ang?.Overexpression of Siat7 A up-regulates Hif-1? and aggravates myocardial hypertrophy in Ang?-induced rats.Conclusions:1.The expressions of Siat7 A and Hif-1? were increased in the cardiac tissue of patients with hypertensive myocardial hypertrophy.2.Siat7 A mediates Hif-1? to promote cardiomyocyte hypertrophy either in vitro or in vivo.3.Hif-1? m RNA expression remains unchanged in Ang?-induced cardiomyocyte hypertrophy. |
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