Regulation Of MicroRNA-34a On Myosin Heavy Chain αExpression In Rats With Cardiac Hypertrophy

Background and ObjectiveMicroRNAs(miRNAs) are highly conserved short single-stranded non-codingRNAs that target specific complementary sequences mostly in the3ˊuntranslatedregions and exert biological functions by post-transcriptional regulation of geneexpression in a sequence-specific manner. Recent studies have revealed expressionsignatures of miRNAs associated with pathological cardiac hypertrophy in humansand mouse models of heart disease.Cardiac hypertrophy is a physiological adaptive response of the heart to diversepathophysiological stimuli,such as hemodynamic overloaded,ischemia,hypoxia, infla-mmation,and the endocrine disorder,which could promote mocyte hypertrophy,reex-pressing fetal gene program and remodeling the extracellular matrix. Alterations ofthe structure and function of myocardial hypertrophy is significantly related withreexpressing of fetal gene,down-regulation of α-myosin heavy chain(α-MHC),up-regulation of β-myosin heavy chain (β-MHC).Decrease of α-MHC level is one ofthe common hallmark of cardiac hypertrophy and heart failure.Althought the targetgenes and mechanism is unknown, research has shown that down-regulation ofmicroRNA-34a expression in the rat model of pathological remodeling, can inhibit myocardial hypertrophy process and improve heart function. After searching throughthe miRNAs target gene prediction website Targetscan, American National Center forBiotechnology Information gene sequence database GenBank,the result indicates thatα-MHC expression gene may be regulated by miRNA-34a.For the advanced study,cardiac hypertrophy rats’ model were made by abdominal aortic constriction (AAC)to test the regulation effects of miRNA-34a on the α-MHC expression andhypertrophy process in the left ventricle hypertrophy tissue.MethodsThe cardiac hypertrophy rats’ models were established by abdominal aorticconstriction (AAC), and40SD rats were randomly divided into4groups.①AACrats with LNA-antimiR-34a (ant-34a/AAC) group,②AAC rats withLNA-control-34a (con/AAC) group, and③sham operation rats withLNA-antimiR-34a (ant-34a/SH) group,④con/SH group. n=10in each group. With8weeks treatment, the surviving conditions were6in ant-34a/AAC group,7incon/AAC group,8in ant-34a/SH group, and8in con/SH group. The left ventricularsystolic pressure (LVSP), left ventricular end-diastolic pressure(LVEDP),themaximum changing rate of pressure (±LVdp/dt)max, heart weight index (HM/BM)and cardiac index (LVM/BM) were calculated, the pathological changes ofmyocardial tissue was observed and the expressions of miRNA-34a and α-MHC inthe left ventricular tissue were analyzed.ResultsCompared with con/AAC group, the ant-34a/AAC group had decreased HM/BM,LVSP, LVEDP and miRNA-34a expression, increased (±LVdp/dt)max and α-MHCexpression, all P<0.05. Compared with con/AAC group, the con/SH group showeddecreased HM/BM, LVSP, LVEDP and miRNA-34a expression, increased(±LVdp/dt)max and α-MHC expression, all P<0.05. Compared with con/SH group,the ant-34a/SH group presented decreased miRNA-34a expression and increasedα-MHC expression, both P<0.05; the HM/BM, LVSP, LVEDP and (±LVdp/dt)max were similar, all P>0.05ConclusionsThe rats of left ventricular hypertrophy with overloaded pressure had increasedmiRNA-34a and decreased α-MHC expression, LNA-antimiR-34a could elevateα-MHC expression and therefore, reduce or delay the myocardial hypertrophy andimprove the cardiac function.