Rho/Rho-kinase is involved in the synthesis of tissue factor in human monocytes

Nagata, Kenji; Ishibashi, Toshiyuki; Sakamoto, Takayuki; Ohkawara, Hiroshi; Shindo, Joji; Yokoyama, Keiko; Sugimoto, Koichi; Sakurada, Sotaro; Takuwa, Yoh; Nakamura, Shin; Teramoto, Tamio; Maruyama, Yukio

doi:10.1016/s0021-9150(01)00750-x

Cited by 33 publications

(32 citation statements)

References 47 publications

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“…We also showed that both hydrophilic and lipophilic statins suppress molecular expression, including tissue factor and plasminogen activator inhibitor-1, by depletion of cellular geranylgeranylpyrophosphate (GGPP) 16,[26][27][28] . Taken together with other reports [29][30][31] , our previous study clearly demonstrated the exact mechanism of the pleiotropic effect that statins rapidly blocks the activation of unprocessed GDP-RhoA by inhibiting geranylgeranylation 9) .…”

Section: Discussionmentioning

confidence: 94%

RhoA and Rac1 Changes in the Atherosclerotic Lesions of WHHLMI Rabbits

Ohkawara¹,

Ishibashi²,

Shiomi

et al. 2009

JAT

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Aim:The activation of RhoA and Rac1 is crucial for the pathogenesis of atherosclerosis. This study investigated the changes of unprocessed and mature forms of RhoA and Rac1 in the progression of atherosclerosis. Methods: Unprocessed and geranylgeranylated forms of RhoA and Rac1 in aortic atherosclerotic lesions were separated by the Triton X-114 partition method using Watanabe heritable hyperlipidemic (WHHLMI) rabbits prone to myocardial infarction. The activation of RhoA and Rac1 was determined by membrane translocation and pull-down assays. Results: The levels of unprocessed RhoA and Rac1 of the aortas were higher at 7 months than 3 months, accompanied by increased levels of total RhoA and Rac1. Membrane-bound RhoA and Rac1 levels of the aortas at 7 months were significantly increased compared with those at 3 months, consistent with the results of GTP-loading. Unprocessed and activated forms of RhoA and Rac1 had gradually decreas at 15 and 24 months compared to 7 months. Conclusions: We show evidence of marked increases in unprocessed RhoA and Rac1 with enhanced activities in the progression of atherosclerosis in WHHLMI rabbits. This is important for better understanding of the pathogenesis of hyperlipidemia-dependent atherosclerosis.

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Section: Discussionmentioning

confidence: 94%

RhoA and Rac1 Changes in the Atherosclerotic Lesions of WHHLMI Rabbits

Ohkawara¹,

Ishibashi²,

Shiomi

et al. 2009

JAT

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“…It has been revealed that Rho/Rho kinase is associated with the generation of TF (Nagata et al, 2002) and can regulate the expression of TF. The Rho/Rho kinase signaling pathway includes Rho protein, Rho kinase, myosin phosphatase, etc.…”

Section: Discussionmentioning

confidence: 99%

Department of Tea Science, Zhejiang University, Hangzhou 310058, P. R. China.

Jiang¹,

Kang²,

Yuan³

et al. 2011

Afr. J. Pharm. Pharmacol.

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To investigate the regulatory role of RhoA/Rho kinase in the effects of fluvastatin (Flu) on the tumor necrosis factor-(TNF-) induced expression of tissue factor (TF) in human umbilical vein endothelial cells (HUVECs) which may provide basis for the prevention of arterial thrombosis, HUVECs in logarithmic phase were divided into TNF-group, Flu group and TNF-+Flu group. enzyme-linked immunosorbent assay (ELISA), real time polymerase chain reaction (RT-PCR) and western blot assay were employed to detect the content of TF, messenger ribonucleic acid (mRNA) expression of TF and protein expressions of TF and activated RhoA, respectively. Then, angiotensin II (Ang II) and Y27632 were used to treat these cells which were then divided into control group, TNF+Ang II group, AngII group, TNF-group and TNF-+Y27632 group. Western blot assay was performed to detect the protein expression of TF. After TNF-treatment, the content and mRNA and protein expressions of TF were markedly increased when compared with the control group (P<0.05). However, the content and mRNA and protein expressions of TF in Flu group were significantly lower than those in TNF-group (P<0.05). Our results showed TNF-could induce TF expression in HUVECs and activate RhoA, which, however, were inhibited by Flu. Ang II treatment could increase the TNF-induced TF expression in HUVECs which however was inhibited Y27632. Flu could effectively inhibit the TNF-induced protein and mRNA expressions of TF in HUVECs in which RhoA/Rho signaling pathway may play an important role.

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“…RhoA proteins are modulators of gene expression, adhesion, and migration of activated macrophages, which also play critical roles in inflammatory signal pathways, such as those required for activation of NF-B (31). In addition, inhibition of Rho/Rho kinase proteins down-regulates the synthesis of TF by cultured human monocytes, and statins (known immunoregulatory and antithrombotic compounds that are now being experimentally tested in APS patients) suppress the synthesis of TF mediated by inhibition of Rho activity (32). Agonists reported to activate Rho proteins in vascular cells include thrombin, endothelin 1, and angiotensin.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis in monocytes of antiphospholipid syndrome patients: Deregulation of proteins related to the development of thrombosis

López‐Pedrera¹,

Cuadrado²,

Herández³

et al. 2008

Arthritis & Rheumatism

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Objective. Antiphospholipid antibodies (aPL) are closely related to the development of thrombosis, but the exact mechanism(s) leading to thrombotic events remains unknown. In this study, using proteomic techniques, we evaluated changes in protein expression of monocytes from patients with antiphospholipid syndrome (APS) related to the pathophysiology of the syndrome.Methods. Fifty-one APS patients were included. They were divided into 2 groups: patients with previous thrombosis, and patients with recurrent spontaneous abortion. As controls, we studied patients with thrombosis but without aPL, and age-and sex-matched healthy subjects.Results. The proteins that were more significantly altered among monocytes from APS patients with thrombosis (annexin I, annexin II, protein disulfide isomerase, Nedd8, RhoA proteins, and Hsp60) were functionally related to the induction of a procoagulant state as well as to autoimmune-related responses. Proteins reported to be connected to recurrent spontaneous abortion (e.g., fibrinogen and hemoglobin) were also determined to be significantly deregulated in APS patients without thrombosis. In vitro treatment with IgG fractions purified from the plasma of APS patients with thrombosis changed the pattern of protein expression of normal monocytes in the same way that was observed in vivo for monocytes from APS patients with thrombosis.

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Rho/Rho-kinase is involved in the synthesis of tissue factor in human monocytes

Cited by 33 publications

References 47 publications

RhoA and Rac1 Changes in the Atherosclerotic Lesions of WHHLMI Rabbits

RhoA and Rac1 Changes in the Atherosclerotic Lesions of WHHLMI Rabbits

Department of Tea Science, Zhejiang University, Hangzhou 310058, P. R. China.

Proteomic analysis in monocytes of antiphospholipid syndrome patients: Deregulation of proteins related to the development of thrombosis

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