Attenuation of Myocardial Fibrosis Using Molecular Hydrogen by Inhibiting the TGF-β Signaling Pathway in Spontaneous Hypertensive Rats
by Libo Liu, Qian Shi, Xiaohong Liu, Xiuchang Li, Yanmin Li
Abstract:
Background: Previous studies have shown that hydrogen (H2) can antagonize the fibrosis of various organs. We investigated whether hydrogen-rich saline (HRS) can attenuate myocardial fibrosis in spontaneously hypertensive rats (SHR) and clarified the mechanisms involved. Methods: We examined the effect of HRS and pirfenidone (PFD) on myocardial fibrosis in SHR. Systolic blood pressure, left ventricular mass index (LVMI) and heart weight index (HWI) were measured, Masson trichrome staining was performed. We assessed the role of superoxide dismutase (SOD), malondialdehyde (MDA), Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, and tissue inhibitors of metalloproteinases (TIMPs) in myocardium. We detected the concentrations of procollagen type-I C-terminal propeptide (PICP), procollagen type-III N-terminal propeptide (PIIINP), and angiotensin II (AngII) in rat serum. Furthermore, the relative protein levels of the TGFβ/Smad pathway were tested. Results: We discovered that HRS decreases LVMI (P<0.05) and HWI(P<0.05) in vivo. Compared to model group, HRS decreases the level of collagen volume fraction(P<0.0001), collagen I(P<0.001), and collagen III(P<0.001) in myocardium, and Ang II(P<0.05), PICP(P<0.001), and PIIINP(P<0.05) in serum. In addition, HRS down-regulates the expression of MDA(P<0.01), α-SMA(P<0.05), and TIMPs(P<0.05), and increased SOD(P<0.05). Furthermore, HRS down-regulated the expression levels of TGF-β1(P<0.0001), Smad3(P<0.0001), and Smad2/3(P0.05). PFD had similar effect compared with HRS and control group. Conclusions: HRS reduced oxidative stress and improved myocardial collagen content, which may be related to inhibition of the TGF-β signaling pathway.This suggests that HRS is an effective therapeutic strategy for myocardial fibrosis.
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https://doi.org/10.1093/ajh/hpab159
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