Frontiers in Physiology (May 2020)
Impact of Bilateral Sympathetic Stellate Ganglionectomy on TGF-β1 Signaling Pathway in Rats With Chronic Volume Overload
Abstract
Background: We previously reported that bilateral sympathetic stellate ganglionectomy attenuated cardiac remodeling and fibrosis in rats with chronic volume overload. Transforming growth factor beta 1 (TGF-β1) is a polypeptide member of the transforming growth factor beta superfamily of cytokines and actively involved in many pathological processes of cardiovascular diseases. The present study explored the impact of bilateral sympathetic stellate ganglionectomy on the TGF-β1 pathway in this model.Methods and Results: Male Sprague–Dawley rats were randomly divided into sham (S) group, abdominal aorta-cava fistula (AV) group, and bilateral sympathetic stellate ganglionectomy after abdominal aorta-cava fistula (AD) group. Twelve weeks after the abdominal aorta-cava fistula surgery, the myocardial expressions of norepinephrine (NE) and hydroxyproline were significantly higher, while acetylcholine was downregulated in the AV group compared to the S group; the above changes were partly reversed in the AD group. The myocardial expression of TGF-β1 and activity of Smad2/3 phosphorylation were also upregulated in the AV group compared to the S group, which could be reversed by bilateral sympathetic stellate ganglionectomy. In vitro, the TGF-β1 expression in cultured myocardial fibroblasts and the proliferation of myocardial fibroblasts were significantly increased post-stimulation with NE in a dose-dependent manner, and these effects could be blunted by co-treatment with a TGF-β1 inhibitor.Conclusion: Our study results indicate that stellate ganglionectomy decreases cardiac norepinephrine release, which leads to decreased TGF-β1 release and reduced fibrosis in rats with chronic volume overload.
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