scholarly journals Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells

2008 ◽  
Vol 7 (1) ◽  
pp. 36 ◽  
Author(s):  
Alokkumar Pathak ◽  
Renyi Zhao ◽  
Jianhua Huang ◽  
George A Stouffer
2003 ◽  
Vol 285 (5) ◽  
pp. C1330-C1338 ◽  
Author(s):  
M. Sajid ◽  
R. Zhao ◽  
A. Pathak ◽  
S. S. Smyth ◽  
G. A. Stouffer

αvβ3-Integrin antagonists reduced neointimal formation following vascular injury in eight different animal models. Because α-thrombin contributes to neointimal formation, we examined the hypothesis that αvβ3-integrins influence α-thrombin-induced signaling. Cultured rat aortic smooth muscle cells (RASMC) expressed αvβ3-integrins as demonstrated by immunofluorescence microscopy and fluorescence-activated cell sorting analysis. Proliferative responses to α-thrombin were partially inhibited by anti-β3-integrin monoclonal antibody F11 and by cyclic RGD peptides. Immunofluorescence microscopy showed that α-thrombin stimulated a rapid increase in the formation of focal adhesions as identified by vinculin staining and that this effect was partially inhibited by αvβ3 antagonists. β3-Integrin staining was diffuse in quiescent RASMC and did not concentrate at sites of focal adhesions following thrombin treatment. α-Thrombin elicited a time-dependent increase in activation of c-Jun NH2-terminal kinase-1 (JNK1) and in tyrosine phosphorylation of focal adhesion kinase (FAK). αvβ3-Integrin antagonists partially inhibited increases in JNK1 activity but had no effect on FAK phosphorylation. In SMC isolated from β3-integrin-deficient mice, focal adhesion formation was impaired in response to thrombin but not sphingosine-1-phosphate, a potent activator of Rho. In summary, αvβ3-integrins play an important role in α-thrombin-induced proliferation and focal adhesion formation in RASMC.


1998 ◽  
Vol 274 (5) ◽  
pp. H1613-H1619 ◽  
Author(s):  
Kuljeet Kaur ◽  
Jian Yao ◽  
Xiaolei Pan ◽  
Carolyn Matthews ◽  
Aviv Hassid

Our laboratory has previously reported that the antimitogenic effect of nitric oxide (NO) in primary cultures of rat aortic smooth muscle cells may be attributed to activation of protein tyrosine phosphatase and dephosphorylation of protein phosphotyrosine [G. S. Dhaunsi, C. Matthews, K. Kaur, and A. Hassid. Am. J. Physiol. 272 ( Heart Circ. Physiol. 41): H1342–H1349, 1997]. The goal of the current study was to investigate the role of cytoplasmic Ca in this process and to identify protein substrates that are dephosphorylated by treatment with NO. Treatment of primary rat aortic smooth muscle cell cultures with the NO donor S-nitroso- N-acetylpenicillamine (SNAP) decreased cytoplasmic Ca levels and elicited phosphotyrosine dephosphorylation. Both effects were mimicked by the extracellular and intracellular Ca chelators ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid (EGTA) and 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA), respectively, and by the Ca channel blocker nifedipine. Conversely, elevation of cytoplasmic Ca via the use of the Ca ionophore A-23187 or high extracellular K+prevented or attenuated SNAP-induced dephosphorylation. Both BAPTA and nifedipine also decreased DNA synthesis, providing further evidence to link dephosphorylation to antimitogenesis. Two of the proteins dephosphorylated by treatment of cells with NO or EGTA were identified as the focal adhesion proteins, cortactin and paxillin. These results indicate that NO-induced dephosphorylation of protein phosphotyrosine is mediated by reduction of cytoplasmic Ca and suggest that dephosphorylation of focal adhesion proteins may be of relevance to the antimitogenic effect of NO.


2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.


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