Epigallocatechingallate attenuates myocardial injury in a mouse model of heart failure through TGF‑β1/Smad3 signaling pathway

Abstract

The present study aimed to assess the protective effect of epigallocatechingallate (EGCG) against myocardial injury in a mouse model of heart failure and to determine the mechanism underlying regulation of the transforming growth factor-β1/mothers against decapentaplegic homolog 3 (TGF-β1/Smad3) signaling pathway. Mouse models of heart failure were established. Alterations in ejection fraction, left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs) were measured by echocardiography. Pathological alterations of myocardial tissue were determined by hematoxylin and eosin, and Masson staining. The levels of serum brain natriuretic peptide (BNP), N-terminal-proBNP, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, malondialdehyde, superoxide dismutase and glutathione peroxidase were detected with ELISA. Expression of collagen I, collagen III were detected by western blotting and reverse transcription quantitative polymerase chain reaction. Transforming growth factor-β1 (TGF-β1), Smad3, phosphorylated (p)-Smad3, apoptosis regulator BAX (Bax), caspase-3 and apoptosis regulator Bcl2 in mouse cardiac tissue were measured by western blotting. P-smad3 and TGF-β1 were measured by immunofluorescence staining. EGCG reversed the alterations in LVIDd and LVIDs induced by establishment of the model of heart failure, increased ejection fraction, inhibited myocardial fibrosis, attenuated the oxidative stress, inflammatory and cardiomyocyte apoptosis and lowered the expression levels of collagen I and collagen III. Following treatment with TGF-β1 inhibitor, the protective effect of EGCG against heart failure was attenuated. The results of the present study demonstrated that EGCG can inhibit the progression and development of heart failure in mice through inhibition of myocardial fibrosis and reduction of ventricular collagen remodeling. This protective effect of EGCG is likely mediated through inhibition of TGF-β1/smad3 signaling pathway.

Various aspects of inflammation in heart failure

“…Recent animal studies confirm that EGCG significantly inhibits the inflammation in HF by disrupting the functioning of this particular signalling pathway. This correlates with the reduction in plasma concentrations of BNP and NT-proBNP, with improvement of left ventricular systolic function and of left ventricular dimensions, as well as with a survival index in this group of animals with HF [58]. The results of these studies give a preliminary theoretical basis for the treatment of the TGF-Beta1/Smad3 signalling pathway as a potential therapeutic target in HF.…”

“…In the animal HF model, it was also confirmed that the intensity of the inflammatory process within the myocardium is significantly reduced by inhibiting the TGF-Beta1/Smad3 signalling pathway [58]. Elevated serum concentrations of proinflammatory cytokines such as interleukin-1Beta (IL-1Beta), IL-6 and TNF-alpha, which are typical in HF, were significantly reduced by treatment with epigallocatechin gallate (EGCG), a substance that strongly inhibits the TGF-Beta1/Smad3 signalling pathway [58]. EGCG is a catechin, i.e.…”

“…In addition, the inhibition of the TGF-Beta1/ Smad3 signalling pathway causes a reduction in plasma concentrations of pro-inflammatory cytokines such as IL-1Beta, IL-6 or TNF-alpha, all of which are elevated in HF. [58]. Increased expression of miR24 has been shown to inhibit the expression of TGF-Beta1 in CFs [89].…”

“…a monomeric aglycone, which belongs to the group of polyphenol compounds belonging to flavonoids. EGCG is obtained mainly from leaves or buds of Camellia sinensis [58]. EGCG is also common in many foods such as apples, apricots, cocoa, black and green tea, red wine and legumes [59].…”

Effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure by regulating TGF-β1/Smad3 signaling pathway

“…The results showed that when we inhibited this pathway, the apoptosis rate of cardiomyocytes induced by H/R reduced obviously, and the Bax and activated Cle-Caspase-3 protein expression levels reduced dramatically, but the Bcl-2 protein expression increased greatly. Research [26] has also confirmed that the apoptosis rate of cardiomyocytes can be reduced by inhibiting this pathway in HF mouse model. This also confirms our conclusion.…”