Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells

2010 ◽  
Vol 118 (3) ◽  
pp. 221-230 ◽  
Author(s):  
Bao-Wei Wang ◽  
Hang Chang ◽  
Kou-Gi Shyu
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
P38 Mapk ◽  
Vascular Smooth Muscle Cells ◽  
Promoter Activity ◽  
Muscle Cells ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Pre Treatment

Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen-activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N-acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N-acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3)-binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.

scholarly journals SIRT1 and FOXO Mediate Contractile Differentiation of Vascular Smooth Muscle Cells under Cyclic Stretch

2015 ◽  
Vol 37 (5) ◽  
pp. 1817-1829 ◽  
Author(s):  
Kai Huang ◽  
Zhi-Qiang Yan ◽  
Dan Zhao ◽  
Si-Guo Chen ◽  
Li-Zhi Gao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Underlying Mechanisms

Background/Aims: Physiological mechanical stretch in vivo helps to maintain the quiescent contractile differentiation of vascular smooth muscle cells (VSMCs), but the underlying mechanisms are still unclear. Here, we investigated the effects of SIRT1 in VSMC differentiation in response to mechanical cyclic stretch. Methods and Results: Rat VSMCs were subjected to 10%-1.25Hz-cyclic stretch in vitro using a FX-4000T system. The data indicated that the expression of contractile markers, including α-actin, calponin and SM22α, was significantly enhanced in VSMCs that were subjected to cyclic stretch compared to the static controls. The expression of SIRT1 and FOXO3a was increased by the stretch, but the expression of FOXO4 was decreased. Decreasing SIRT1 by siRNA transfection attenuated the stretch-induced expression of contractile VSMC markers and FOXO3a. Furthermore, increasing SIRT1 by either treatment with activator resveratrol or transfection with a plasmid to induce overexpression increased the expression of FOXO3a and contractile markers, and decreased the expression of FOXO4 in VSMCs. Similar trends were observed in VSMCs of SIRT1 (+/-) knockout mice. The overexpression of FOXO3a promoted the expression of contractile markers in VSMCs, while the overexpression of FOXO4 demonstrated the opposite effect. Conclusion: Our results indicated that physiological cyclic stretch promotes the contractile differentiation of VSMCs via the SIRT1/FOXO pathways and thus contributes to maintaining vascular homeostasis.

scholarly journals Downregulation of miRNA-1-3p modulates cyclic stretch-mediated proliferation of vascular smooth muscle cells through regulation of ETS-1

2020 ◽  
Vol 72 (4) ◽  
pp. 587-598
Author(s):  
Xizhen Wang ◽  
Aihua Li ◽  
Ruikang Duan ◽  
Bin Zhang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Collagen Type ◽  
Muscle Cells ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Luciferase Reporter ◽  
Type I

Mechanical stretch modulates the proliferation of vascular smooth muscle cells (VSMCs) and plays an important role in the pathogenesis of hypertension, but the underlying mechanisms are unclear. We investigated the role of microRNA- 1-3p (miRNA-1-3p) on the proliferation of VSMCs induced by mechanical cyclic stretch. Our data show that miRNA-1-3p is downregulated in the aorta of the spontaneous hypertension rat (SHR). Pathological mechanical stretch at 15% suppressed the expression of miRNA-1-3p, calponin and SM22, but enhanced the proliferation of VSMCs as well as the expression of the V-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1), collagen type I alpha (Col-1a), collagen type III alpha (Col-3a) and elastin. Overexpression of miRNA-1-3p inhibited cell proliferation and induced the expression of calponin and SM22, but decreased the expression of ETS-1, Col-1a, Col-3a and elastin. Mechanical stretch at 15% combined with losartan treatment increased the expression of miRNA-1-3p, calponin and SM22, and decreased the expression of ETS-1, Col-1a and Col-3a. Dual luciferase reporter assays revealed ETS-1 as a direct target of miRNA-1-3p. These findings suggest that miRNA-1-3p regulates VSMC function through ETS-1 regulation during hypertension-induced vascular remodeling. MiRNA-1-3p may be a viable therapeutic target for hypertension.

scholarly journals The involvement of aldosterone in cyclic stretch-mediated activation of NADPH oxidase in vascular smooth muscle cells

2009 ◽  
Vol 32 (8) ◽  
pp. 690-699 ◽  
Author(s):  
Takahiro Ohmine ◽  
Yoshikazu Miwa ◽  
Fumi Takahashi-Yanaga ◽  
Sachio Morimoto ◽  
Yoshihiko Maehara ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Nadph Oxidase ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cyclic Stretch

scholarly journals 17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

2010 ◽  
Vol 45 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Ping Jiang ◽  
Jinwen Xu ◽  
Shuhui Zheng ◽  
Jinghe Huang ◽  
Qiuling Xiang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
P38 Mapk ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Pyrrolidine Dithiocarbamate ◽  
17Β Estradiol ◽  
Anti Inflammatory

Atherosclerosis is an inflammatory disease where lipopolysaccharide (LPS) triggers the release of inflammatory cytokines that accelerate its initiation and progression. Estrogen has been proven to be vasoprotective against atherosclerosis; however, the anti-inflammatory function of estrogen in the vascular system remains obscure. In this study, we investigated the effect of estrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1; listed as CCL2 in the MGI database) production in vascular smooth muscle cells (VSMCs). LPS significantly enhances MCP-1 production and this is dependent on nuclear factor κ B (NFκB) signaling, since the use of NFκB inhibitor pyrrolidine dithiocarbamate or the silencing of NFκB subunit p65 expression with specific siRNA largely impairs LPS-enhanced MCP-1 production. On the contrary, 17β-estradiol (E2) inhibits LPS-induced MCP-1 production in a time- and dose-dependent manner, which is related to the suppression of p65 translocation to nucleus. Furthermore, p38 MAPK is rapidly activated in response to LPS, while E2 markedly inhibits p38 MAPK activation. Transfection with p38 MAPK siRNA or the use of p38 MAPK inhibitor SB203580 markedly attenuates LPS-stimulated p65 translocation to nucleus and MCP-1 production, suggesting that E2 suppresses NFκB signaling by the inactivation of p38 MAPK signaling. LPS promotes VSMCs migration and this is abrogated by MCP-1 antibody, implying that MCP-1 may play a major role as an autocrine factor in atherosclerosis. In addition, E2 inhibits LPS-promoted cell migration by downregulation of MCP-1 production. Overall, our results demonstrate that E2 exerts anti-inflammatory property antagonistic to LPS in VSMCs by reducing MCP-1 production, and this effect is related to the inhibition of p38 MAPK/NFκB cascade.

Sign in / Sign up

Export Citation Format

Share Document