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Thromb Haemost 2008; 100(06): 1155-1165
DOI: 10.1160/TH08-02-0104
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

High glucose conditions induce upregulation of fractalkine and monocyte chemotactic protein-1 in human smooth muscle cells

Elena Dragomir
1   Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest, Romania
,
Ileana Manduteanu
1   Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest, Romania
,
Manuela Calin
1   Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest, Romania
,
Ana Maria Gan
1   Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest, Romania
,
Daniela Stan
1   Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest, Romania
,
Rory Ryan Koenen
2   Institute for Cardiovascular Molecular Research (IMCAR), University Hospital, Aachen, RWTH Aachen University, Aachen, Germany
,
Christian Weber
2   Institute for Cardiovascular Molecular Research (IMCAR), University Hospital, Aachen, RWTH Aachen University, Aachen, Germany
,
Maya Simionescu
1   Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest, Romania
› Author AffiliationsFinancial support: This work was supported by the Romanian Academy and Ministry of Education and Research grants – CEEX (1423 and 130/2006).
Further Information

Publication History

Received: 22 February 2008

Accepted after major revision: 24 September 2008

Publication Date:
23 November 2017 (online)

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Summary

The major complication of diabetes mellitus is accelerated atherosclerosis that entails an inflammatory process, in which fractalkine and monocyte chemotactic protein-1 (MCP-1) play a key role.We investigated the effect of diabetes-associated high glucose (HG) on these chemokines and signalling mechanisms involved in human aortic smooth muscle cells (SMC). Exposure of SMC to HG resulted in an increase of fractalkine and MCP-1 expression and the activated mitogen-activated protein kinase (MAPK) signalling pathway, a process associated with elevated oxidative stress.Transfection with decoy oligodeoxynucleotides identified the involvement of transcription factors activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) in the observed up-regulation of chemokines. The MAPK inhibitors blocked the phosphorylation of IkBα and c-jun, indicating the role of MAPK in NF-κB and AP-1 activation in SMC under HG conditions.The up-regulation of MCP-1 and fractalkine was associated with increased adhesive interactions between HG-exposed SMC and monocytes. Treatment of HG-exposed SMC with peroxisome proliferator-activated receptors α (PPAR α ) activators (fenofibrate and clofibrate) resulted in a reduction of mRNA and protein expression of MCP-1 and fractalkine.In conclusion, HG upregulates the expression of fractalkine and MCP-1 in SMC leading to increased monocyte-SMC adhesive interactions by a mechanism involving activation of MAPK, activator protein-1 (AP-1) and NF-κB. The increased expression of these two pro-inflammatory chemokines and the ensuing increased adhesion between SMC and monocytes may trigger the inflammatory process associated with further vascular complications of diabetes.

Keywords

Fractalkine - MCP-1 - high glucose - smooth muscle cells - MAPK signalling

 

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