Velvet antler peptide prevents pressure overload-induced cardiac fibrosis via transforming growth factor (TGF)-β1 pathway inhibition.
Velvet antlers (VAs) are commonly used in traditional Chinese medicine and invigorant and contain many functional components for health promotion. The velvet antler peptide sVAP32 is one of active components in VAs; based on structural study, the sVAP32 interacts with TGF-β1 receptors and disrupts the TGF-β1 pathway. We hypothesized that sVAP32 prevents cardiac fibrosis from pressure overload by blocking TGF-β1 signaling. Sprague-Dawley rats underwent transverse aortic constriction (TAC) or a sham operation. After one month, rats received either sVAP32 (15mg/kg/day) or vehicle for an additional one month. TAC surgery induced significant cardiac dysfunction, fibroblast activation and fibrosis; these effects were improved by treatment with sVAP32. In the heart tissue, TAC remarkably increased the expression of TGF-β1 and connective tissue growth factor (CTGF), reactive oxygen species levels, and the phosphorylation levels of Smad2/3 and extracellular signal-regulated kinases 1/2 (ERK1/2). SVAP32 inhibited the increases in reactive oxygen species levels, CTGF expression and the phosphorylation of Smad2/3 and ERK1/2, but not TGF-β1 expression. In cultured cardiac fibroblasts, angiotensin II (Ang II) had similar effects compared to TAC surgery, such as increases in α-SMA-positive cardiac fibroblasts and collagen synthesis. SVAP32 eliminated these effects by disrupting TGF-β1 binding to its receptors and blocking Ang II/TGF-β1 downstream signaling. These results demonstrated that sVAP32 has anti-fibrotic effects by blocking the TGF-β1 pathway in cardiac fibroblasts.
['Zhao|Lihong|L|', 'Mi|Yang|Y|', 'Guan|Hongya|H|', 'Xu|Yan|Y|', 'Mei|Yingwu|Y|']
D000595:Amino Acid Sequence D000804:Angiotensin II D000818:Animals D000999:Antlers D001011:Aorta D001794:Blood Pressure D049109:Cell Proliferation D055513:Connective Tissue Growth Factor D005347:Fibroblasts D005355:Fibrosis D005786:Gene Expression Regulation D006984:Hypertrophy D009206:Myocardium D018384:Oxidative Stress D010455:Peptides D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D015398:Signal Transduction D051899:Smad2 Protein D051900:Smad3 Protein D053773:Transforming Growth Factor beta1 D014661:Vasoconstriction
Velvet antler peptide Cardiac fibrosis TGF-Β1 Transverse aortic constriction Connective tissue growth factor