Thrombin induces production in human umbilical vein endothelial cells

Murakami, Kohji; Ueno, Akemi; Yamanouchi, Kouichi; Kondo, Takao

doi:10.1016/0049-3848(95)00127-d

Cited by 22 publications

(11 citation statements)

References 14 publications

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“…Up-regulation of the GRO-a receptor CXCR2 has not been reported for thrombin or GRO-a. Up-regulation of GRO-a by thrombin has been reported for HUVEC (31). Our data indicate that this is likely to be a general response because it is also up-regulated by thrombin in several tumor cell lines, murine B16F10 and UMCL, and human MCF7 breast and PC3 prostate cell lines.…”

Section: Discussionmentioning

confidence: 49%

“…In melanoma, GRO-a has been shown to have mitogenic as well as angiogenic effects on tumor growth (33). A DU145 human prostate cancer cell line had in vivo growth, which correlated with tumor-derived GRO-a and could be inhibited with anti-GRO-a antibody (31). GRO-a promotes murine squamous cell carcinoma growth, metastasis, and leukocyte infiltration by a host CXCR2-dependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

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Growth-Regulated Oncogene Is Pivotal in Thrombin-Induced Angiogenesis

et al. 2006

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Growth-Regulated Oncogene Is Pivotal in Thrombin-Induced Angiogenesis

et al. 2006

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“…Previous studies have shown that GRO␣ can support monocyte arrest to endothelium in models of inflammation. 19 The relevance of this to atherosclerosis was recently shown by Boisvert et al demonstrating that deficiency of murine GRO␣ was associated with a loss of intimal macrophages and attenuated disease progression in LDLR Ϫ/Ϫ mice. 24 In the present study, we show that the proatherogenic effects of GRO␣ may not be limited to chemotactic and firm adhesionactivating properties.…”

Section: Discussionmentioning

confidence: 99%

“…To this end, inflammatory cytokines (eg, IL-1 and tumor necrosis factor [TNF] ␣), thrombin, oxidized LDL (oxLDL), and shear stress have all been found to induce GRO␣ expression in endothelial cells. [17][18][19][20][21] Shear stress has also been reported to induce GRO␣ expression in murine atherosclerosis, 22 and we have previously reported raised plasma levels of GRO␣ in angina patients. 23 Herein, we extend these findings by identifying GRO␣ as one of the most strongly induced cytokines in PBMCs from CAD patients when compared to healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

A Potential Role of the CXC Chemokine GROα in Atherosclerosis and Plaque Destabilization

Breland

Halvorsen

Hol

et al. 2008

ATVB

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Objective-We examined the role of the CXCR2 ligand growth-related oncogene (GRO) ␣ in human atherosclerosis. Methods and Results-GRO␣ levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GRO␣ was examined in endothelial cells and THP-1 macrophages. Our main findings were: (1) GRO␣ was among the 10 most differentially expressed transcripts comparing peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) and healthy controls. (2) Both patients with stable (nϭ41) and particularly those with unstable (nϭ47) angina had increased plasma levels of GRO␣ comparing controls (nϭ20). (3) We found increased expression of GRO␣ within symptomatic carotid plaques, located to macrophages and endothelial cells. Key Words: atherosclerosis Ⅲ chemokines Ⅲ inflammation Ⅲ endothelium C oronary artery disease (CAD) is a chronic progressive disorder where the pathogenesis is multifactorial and involves lipid deposition, thrombus formation, matrix degradation, and inflammation. In all steps of this process, regulation by inflammatory cytokines seems to play a central role, but there are still issues to be clarified, and the precise mechanisms of action of each of the inflammatory participants have not been elucidated. 1 Chemokines are thought to be important actors in the inflammatory process characterizing atherogenesis and plaque destabilization. Thus, increased expression of IL-8 2 and monocyte chemoattractant protein (MCP)-1 3 has been found within atherosclerotic plaques in humans, and targeted disruption of the genes for MCP-1, 4 CCR2 (ie, MCP-1 receptor), 5 and CXCR2, 6 which binds IL-8, significantly decreases atherosclerotic lesion formation in mice prone to developing atherosclerosis. CXCR2 is 1 of 2 functional IL-8 receptors that also bind other CXC chemokines like growthrelated oncogene (GRO)␣. As no murine IL-8 homologue has been described, 7 but disruption of CXCR2 ameliorates murine atherosclerosis, we believe that other CXCR2 ligands are of importance in this process. This hypothesis is strengthened by the observation that GRO␣ rather than MCP-1 promotes monocyte arrest in inflamed endothelium in apolipoprotein E Ϫ/Ϫ mice. 8 However, although there are several reports on IL-8 in human CAD, few studies have examined the role of other CXCR2 ligands in human atherosclerosis.In the present study, we identified GRO␣ as a potentially important mediator of atherogenesis by using DNA microarrays to identify transcripts for cytokines in peripheral blood mononuclear cells (PBMCs) that were differently expressed in CAD patients and healthy controls. We further examined the possible role of this CXC chemokine in atherosclerosis by several approaches including clinical studies in CAD patients and experimental studies in cells with relevance to atherogenesis. We also examined the Materials and Methods Patients and ControlsIn the initial screening experiments with DNA microarrays and subsequent real-time RT-PCR analyses,...

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“…For example, potential inducers of GRO-␣ and/or IL-8 in atherosclerotic lesion cells include minimally modified or oxidized lowdensity lipoprotein, thrombin, and CD40-CD40 ligand (CD40L) interaction. 11,27,42,43 Thus, suppression of hyperlipidemia, thrombosis, and CD40-CD40L interactions may suppress the progression of established disease by acting in part through suppression of CXCR2 ligand expression. The results presented in this study indicate the need for future investigation of the effects of specific pharmacological and immunological inhibitors of CXCR2, GRO-␣, and possibly of other individual CXCR2 ligands on the course of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulated Expression of the CXCR2 Ligand KC/GRO-α in Atherosclerotic Lesions Plays a Central Role in Macrophage Accumulation and Lesion Progression

Boisvert

Rose

Johnson

et al. 2006

The American Journal of Pathology

172

120

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Macrophage-mediated inflammation is central to atherogenesis. We have determined previously that the CXC chemokine receptor CXCR2 is involved in advanced atherosclerosis. We sought to determine whether one of the ligands of CXCR2, KC/GRO-␣, can also modulate atherogenesis. KC/GRO-␣ ؊/؊ mice were generated and mated with the atherosclerosis-prone LDLR ؊/؊ mice. There was a significant reduction in atherosclerosis in mice lacking KC/GRO-␣; however, this reduction was only approximately half that seen previously in mice lacking CXCR2 in the leukocyte. To determine whether CXCR2 is involved in the early formation of atherosclerosis, leukocyte-specific CXCR2 ؊/؊ chimeric mice on LDLR ؊/؊ background were generated. Early fatty streak lesion formation in these mice was not affected by leukocyte CXCR2 deficiency whereas lesions were less developed in mice lacking leukocyte CXCR2 when atherosclerosis was allowed to progress to the intermediate stage.

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Thrombin induces production in human umbilical vein endothelial cells

Cited by 22 publications

References 14 publications

Growth-Regulated Oncogene Is Pivotal in Thrombin-Induced Angiogenesis

Growth-Regulated Oncogene Is Pivotal in Thrombin-Induced Angiogenesis

A Potential Role of the CXC Chemokine GROα in Atherosclerosis and Plaque Destabilization

Up-Regulated Expression of the CXCR2 Ligand KC/GRO-α in Atherosclerotic Lesions Plays a Central Role in Macrophage Accumulation and Lesion Progression

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