Correlation Between TWEAK And Cardiac Remodeling In Essential Hypertensive Patients

BackgroundHypertension is one of the most common cardiovascular diseases,and has been paid more and more attention because of its high incidence and younger in average age.The main early change of cardiac function in hypertensive is diastolic dysfunction,manifested as myocardial relaxation decreased and stiffness increased.Long term pressure load,structure and functional changes in myocardial cells and the extracellular matrix induce cardiac remodeling,such as left atrial dilatation,left ventricular dilatation and hypertrophy,and eventually lead to arrhythmia,heart failure,sudden cardiac death and other adverse cardiovascular events.Tumor necrosis factor like weak inducer of apoptosis(TWEAK)as one of the members of the TNF superfamily,is a transmembrane homo-trimer for a total length of 249 amino acids,can be hydrolyzed into soluble cytokine with multiple functions by protein furin.The only clear TWEAK receptor is fibroblast growth factor induced early response protein 14(Fn14),TWEAK and Fn14 receptor mediated proliferation,migration,apoptosis,differentiation,angiogenesis and inflammation and other biological processes,and they play an important regulatory role in the pathophysiology of myocardial infarction,heart failure,hypertension and other cardiovascular system diseases.With the development of the study of hypertension and the application of echocardiography in clinical practice,the early cardiac remodeling drived by hypertension has been paid more and more attention.This study detected the expression levels of sTWEAK and Matrix metalloproteinase 1(sMMP-1)in patients with primary hypertension in the peripheral blood,echocardiographic Left atrium diameter(LAD),left atrial volume(LAV),left atrial volume index(LAVI),the early wave of mitral flow(E)and atrial wave of mitral flow(A),and E/A,the ratio of mitral flow early wave to mitral annular early diastolic velocity E/E' and investigated the relationship between TWEAK expressions and cardiac remodeling in essential hypertension.ObjectiveTo investigate the association between tumor necrosis factor-like weak inducer of apoptosis(TWEAK)and cardiac remodeling in essential hypertensive patients.Methods1.A total of 88 hypertensive patients were classified as Hypertension Group,and they were divided into two subgroups according to the serum level of soluble TWEAK(sTWEAK):group with high level of sTWEAK(n=51)and group with low level of sTWEAK(n=37)meanwhile,20 subjects were selected as Control Group.2.The mRNA expressions of TWEAK and Fn14 in PBMCs(peripheral blood mononuclear cells)were detected using real-time PCR(RT-PCR).3.sTWEAK,sMMP-1 and sFn14 were measured by Enzyme Linked Immunosorbent Assay(ELISA).4.Measure echocardiographic parameters as follows:Left atrium diameter(LAD),left atrial volume index(LAV),left atrial volume index(LAVI),The mitral flow peak speeds of early wave(E)and atrial wave(A),and E/A,the lateral wall motion spectrum peak ratio E/E ' of mitral valve ring.Results1.The levels of TWEAK mRNA in hypertensive group were both higher than those in the control group(P<0.05),and compared with the group with low sTWEAK levels,significantly greater than those in the group with high sTWEAK levels(P<0.01).The levels of Fn14 mRNA had no significant statistical difference in different groups.2.The concentrations of sTWEAK and sMMP-1 in the group with low sTWEAK levels were higher than those in the control group(P=0.02;P=0.001),and compared with the group with low sTWEAK levels,significantly greater than those in the group with high sTWEAK levels(P=0.006;P<0.01).The levels of sFn14 had no significant statistical difference in different groups.3.The LAVI?E/E' in the two subgroups were both greater than those in the control group(P<0.05),and these indexes were significantly greater in the group with high sTWEAK levels than those in the group with low sTWEAK levels(P<0.01).4.The sTWEAK and TWEAK mRNA showed a significant positive correlation with sMMP-1,LAVI,E/E' and hs-CRP,respectively(P<0.01).ConclusionTWEAK was up-regulated in essential hypertensive patients;sMMP-1 concentrations were up-regulated in essential hypertensive patients;Cardiac remodeling in essential hypertensive patients was closely correlated with up-regulated TWEAK;TWEAK might induce sMMP-1 to up-regulate and inflammatory reactions to participate in the occurrence of cardiac remodeling.