Tea Polyphenols Regulate Renin-angiotensin-aldosterone System and Transforming Growth Factor-β1/Smads Signaling Pathway in Heart Failure Rats

Abstract

Objective To investigate the effects of tea polyphenols on the renin-angiotensin-aldosterone system and the transforming growth factor-β1(TGF-β1)/Smads signaling pathway in heart failure rats.Methods SD rats were randomly assigned into a sham group,a model group,a captopril group(PC group),and a tea polyphenol group(TP group).The left anterior descending coronary artery was ligated with silk thread to establish the rat model of heart failure after myocardial infarction in the model group,PC group,and TP group,while it was not ligated in the sham group.Echocardiography was used to detect cardiac function.HE staining and Masson staining were conducted for the observation of myocardial pathological changes and myocardial fibrosis,respectively.Immunohistochemistry was employed to detect the expression of collagen Ⅰ and collagen Ⅲ.ELISA kits were used to measure the levels of angiotensin Ⅱ(AngⅡ),aldosterone(ALD),plasma renin activity(PRA),interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Western blotting was employed to determine the protein levels of TGF-β1,phosphorylated Smad2(p-Smad2),Smad2,p-Smad3,and Smad3.Results Compared with the sham group,the model group showed disordered myocardial cells with obvious inflammatory cell infiltration,increased degree of myocardial fibrosis(t=9.748,P=0.001),elevated levels of collagen Ⅰ(t=11.754,P=0.001) and collagen Ⅲ(t=10.573,P=0.001),decreased ejection fraction(EF)(t=13.174,P=0.002) and left ventricular short axis shortening rate(LVFS)(t=11.853,P=0.001),and up-regulated expression of AngⅡ(t=4.246,P=0.001),ALD(t=5.385,P=0.004),PRA(t=4.386,P=0.004),IL-1β(t=4.393,P=0.001),IL-6(t=6.375,P=0.002),and TNF-α(t=4.753,P=0.002),and up-regulated protein levels of TGF-β1(t=6.365,P=0.001),p-Smad2/Smad2(t=13.755,P=0.001),and p-Smad3/Smad3(t=11.657,P=0.002).Compared with the model group,PC and TP alleviated the myocardial pathological changes,decreased the left ventricular end-diastolic diameter(LVEDd)(t=6.367,P=0.003 and t=5.264,P=0.003),left ventricular end-systolic diameter(LVEDs)(t=5.253,P=0.002 and t=5.974,P=0.001),heart mass index(HMI)(t=5.012,P=0.007 and t=4.953,P=0.005),left ventricular mass index(LVMI)(t=5.531,P=0.003 and t=5.483,P=0.004),and the degree of myocardial fibrosis(t=6.734,P=0.001 and t=5.362,P=0.001).Furthermore,they lowered the levels of collagen Ⅰ (t=5.373,P=0.001 and t=4.364,P=0.001) and collagen Ⅲ(t=6.764,P=0.001 and t=4.579,P=0.001),increased EF(t=11.264,P=0.002 and t=10.356,P=0.001) and LVFS(t=8.246,P=0.002 and t=7.824,P=0.001),and down-regulated the expression of AngⅡ(t=3.126,P=0.001 and t=2.853,P=0.001),ALD(t=3.854,P=0.004 and t=3.164,P=0.004),PRA(t=3.126,P=0.004 and t=3.063,P=0.004),IL-1β(t=2.964,P=0.001 and t=2.765,P=0.001),IL-6(t=4.865,P=0.002 and t=4.275,P=0.002),and TNF-α(t=3.146,P=0.002 and t=2.973,P=0.002).In addition,they down-regulated the protein levels of TGF-β1(t=4.657,P=0.001 and t=4.176,P=0.001),p-Smad2/Smad2(t=9.687,P=0.001 and t=6.753,P=0.001) and p-Smad3/Smad3(t=6.477,P=0.002 and t=4.754,P=0.002).Conclusion Tea polyphenols protect rats from heart failure by inhibiting the activation of renin-angiotensin-aldosterone system and TGF-β1/Smads pathway.