Monocyte Chemotactic Protein-1 Expression Is Associated With the Development of Vein Graft Intimal Hyperplasia

Stark, Vida K.; Hoch, John R.; Warner, Thomas F.; Hullett, Debra A.

doi:10.1161/01.atv.17.8.1614

Cited by 70 publications

(67 citation statements)

References 40 publications

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“…An increased mononuclear cell infiltration attracted by increased levels of MCP-1 can enhance both rejection and the development of transplantassociated atherosclerosis (26). Although we cannot exclude subclinical rejections, we found no influence of the MCP-1 variant on acute rejection in our population.…”

Section: Discussioncontrasting

confidence: 46%

A Monocyte Chemoattractant Protein-1 (MCP-1) Polymorphism And Outcome After Renal Transplantation

Krüger¹,

Schröppel

Ashkan

et al. 2002

Journal of the American Society of Nephrology

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Abstract. Among the factors modulating transplant rejection and cardiovascular disease, chemokines and their respective receptors deserve special attention. In this respect, increased expression of MCP-1 and the corresponding receptor CCR2 have been demonstrated in renal transplant rejection and coronary artery disease. The impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function was investigated in 232 patients who underwent transplantation over an 11-yr period. Genomic DNA was genotyped using PCR with sequence-specific primers followed by restriction fragment length polymorphism analysis. Eighteen (7.8%) patients were homozygous for the MCP-1-2518G mutation. The G/G allele of MCP-1 -2518 behaved as a determinant for long-term allograft survival and resulted in reduction of the mean graft survival, as compared with the heterozygous (A/G) or wild-type (A/A) allele (67 Ϯ 14 versus 95 Ϯ 4 mo; Log rank P ϭ 0.0052). The 64I mutation of CCR2 had no effect on kidney graft failure (93 Ϯ 6 and 91 Ϯ 5 mo, respectively; P ϭ 0.81). None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups. In conjunction with these findings, peripheral blood mononuclear cells from kidney transplant recipients carrying the G-allele were characterized by a 2.5-fold higher MCP-1 secretion (P Ͻ 0.05).

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Section: Discussioncontrasting

confidence: 46%

A Monocyte Chemoattractant Protein-1 (MCP-1) Polymorphism And Outcome After Renal Transplantation

Krüger¹,

Schröppel

Ashkan

et al. 2002

Journal of the American Society of Nephrology

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“…Intimal hyperplasia of vein grafts, which involves an exaggerated vascular wound healing response, has been associated with increased MCP-1 levels that may stimulate monocyte infiltration as well as promote endothelial migration. 45 The advent of chemokine peptide antagonists, eg, the 9-76 MCP-1 analogue, which has already been tested in a murine arthritis model, 46,47 may offer encouraging novel approaches in the treatment of inflammatory conditions, restenosis, or angiogenic tumors.…”

Section: Discussionmentioning

confidence: 99%

Expression of CCR2 by Endothelial Cells

Weber¹,

Nelson²,

Gröne³

et al. 1999

ATVB

267

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Abstract-Endothelial cell proliferation and migration may play a central role in angiogenesis, wound healing, and atherosclerosis. Although CXC chemokines can act on endothelial cells by influencing proliferation, an involvement of CC chemokines and endothelial expression of chemokine receptors remains to be elucidated. Reverse transcriptionpolymerase chain reaction, RNase protection, Western blot, and flow cytometric analysis showed that human umbilical vein endothelial cells express mRNA and surface protein of the monocyte chemotactic protein-1 (MCP-1) receptor CCR2, which was upregulated by inflammatory cytokines. MCP-1 induced migration of endothelial cells in a transwell assay, which was inhibited by the 9-76 MCP-1 receptor antagonist. Increased secretion of MCP-1 or interleukin-8, but not RANTES, on endothelial injury suggested a functional role of CCR2 in wound repair as measured by ELISA. After mechanical injury to endothelial monolayers, which spontaneously closed within 24 hours, wound repair was delayed by the 9-76 antagonist and by a blocking monoclonal antibody to MCP-1, but not to interleukin-8, and was improved by exogenous MCP-1. This was confirmed by quantification of cell migration into the wound area, whereas proliferation and viability were unaltered by MCP-1 or its analogue. Notably, immunohistochemistry of inflamed tissue revealed CCR2 staining on arterial, venous, and venular endothelium affected by cellular infiltration. This is the first demonstration of endothelial CCR2 expression ex vivo, inferring its involvement in inflammatory conditions. Thus endothelial cells express functional CCR2 that may have important implications for endothelial wound repair and inflammatory reactions.

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“…Although vein grafts are commonly used as conduits in cardiac and vascular surgery, 10 their use is commonly complicated by intimal hyperplasia and accelerated atherosclerosis, which cause late failure rates of up to 40% of grafts within 10 years of surgery. 11 The process of vein grafting leads to activation of MAP kinases, 12,13 endothelial expression of adhesion molecules 14 and chemokines, 15 and recruitment of inflammatory cells within 6 to 24 hours after surgery. 16,17 It has been suggested that the inflammatory process contributes to pathogenesis because vein graft disease can be reduced by depletion of macrophages 18 or by genetic deletion of proinflammatory genes such as intercellular adhesion molecule-1 19 or the p55 tumor necrosis factor receptor.…”

Section: Clinical Perspective On P 532mentioning

confidence: 99%

Dexamethasone Arterializes Venous Endothelial Cells by Inducing Mitogen-Activated Protein Kinase Phosphatase-1

et al. 2011

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Background-Vein grafting in coronary artery surgery is complicated by a high restenosis rate resulting from the development of vascular inflammation, intimal hyperplasia, and accelerated atherosclerosis. In contrast, arterial grafts are relatively resistant to these processes. Vascular inflammation is regulated by signaling intermediaries, including p38 mitogen-activated protein (MAP) kinase, that trigger endothelial cell (EC) expression of chemokines (eg, interleukin-8, monocyte chemotactic protein-1) and other proinflammatory molecules. Here, we have tested the hypothesis that p38 MAP kinase activation in response to arterial shear stress (flow) may occur more readily in venous ECs, leading to greater proinflammatory activation. Methods and Results-Comparative reverse-transcriptase polymerase chain reaction and Western blotting revealed that arterial shear stress induced p38-dependent expression of monocyte chemotactic protein-1 and interleukin-8 in porcine jugular vein ECs. In contrast, porcine aortic ECs were protected from shear stress-induced expression of p38-dependent chemokines as a result of rapid induction of MAP kinase phosphatase-1. However, we observed with both cultured porcine jugular vein ECs and perfused veins that venous ECs can be protected by brief treatment with dexamethasone, which induced MAP kinase phosphatase-1 to suppress proinflammatory activation. 1 This process is coordinated by the simultaneous activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinases 2 and nuclear factor-B (NF-B) 3 signaling pathways, which cooperate to induce and stabilize proinflammatory transcripts in vascular ECs. 4,5 Clinical Perspective on p 532 Conclusions-ArterialThe susceptibility of blood vessels to inflammatory processes varies according to their anatomic location. This has been attributed to local differences in hemodynamics 6,7 ; differences in the structure and physiology of blood vessels also play an important role. 8,9 This is exemplified in bypass grafting in which arteries and veins respond differently to arterial flow. Although vein grafts are commonly used as conduits in cardiac and vascular surgery, 10 their use is commonly complicated by intimal hyperplasia and accelerated atherosclerosis, which cause late failure rates of up to Received October 14, 2009; accepted November 15, 2010. From the British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute (M.Z., L.A.L., H.C., O.R., J.C.M., D.O.H., P.C.E.), Department of Cardiothoracic Surgery (P.P.P., J.R.A., J.W.M., A.T.C.), Department of Bioengineering (R.K., N.F.), and Department of Biosurgery and Surgical Technology (T.A.) To gain insight into intrinsic molecular mechanisms underlying the differential responses of arteries and veins to grafting, we compared the effects of arterial shear stress on proinflammatory activation of venous and arterial ECs. We found that arterial but not venous ECs were protected from proinflammatory activation in response to the rapid induction of high...

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Monocyte Chemotactic Protein-1 Expression Is Associated With the Development of Vein Graft Intimal Hyperplasia

Cited by 70 publications

References 40 publications

A Monocyte Chemoattractant Protein-1 (MCP-1) Polymorphism And Outcome After Renal Transplantation

A Monocyte Chemoattractant Protein-1 (MCP-1) Polymorphism And Outcome After Renal Transplantation

Expression of CCR2 by Endothelial Cells

Dexamethasone Arterializes Venous Endothelial Cells by Inducing Mitogen-Activated Protein Kinase Phosphatase-1

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