Methylglyoxal stimulated proliferation of vascular smooth muscle cell through enhanced cytoplasmic CDK2 activity

• Published in: The FASEB journal 2006-03, Vol.20 (4), p.A461-A461
• Main Authors: Chang, Tuanjie, Wang, Rui, Wu, Lingyun
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A461-a

Elevated MG levels and over‐proliferation of vascular smooth muscle cells (VSMCs) in spontaneously hypertensive rats has been reported. Present study investigated the effect of MG on VSMCs proliferation. Application of MG at the range of 0.01 to 10 μM significantly increased DNA synthesis and proliferation of cultured VSMCs, which was abolished by co‐application of N‐acetylcysteine (NAC) or superoxide dismutase (SOD). Cyclin‐dependent kinase 2 (CDK2) activity in cytoplasmic fraction, but not nuclear fraction, of MG‐treated cells was increased, as compared with that of control cells. Activity of cyclin A‐CDK2 complexes, but not cyclin E‐CDK2, was responsible for the increased cytoplasmic CDK2 activity. Protein levels of CDK2, cyclin A, cyclin E and phosphorylation at residue Thr160 of CDK2 were not altered by MG treatment. However, phosphorylation at residue Tyr15 of CDK2 was significantly decreased in MG‐treated cells compared to control cells, which may account the increased cytoplasmic CDK2 activity. Increased cytoplasmic CDK2 activity and decreased phosphorylation on Tyr15 of CDK2 in MG‐treated cells were prevented by co‐application of NAC or SOD. In conclusion, MG at physiologically relevant concentrations stimulated VSMCs proliferation through an enhanced cytoplasmic CDK2 activity. Increased MG level, therefore, may underscore increased proliferation of VSMC in some cardiovascular disorders. (Grants from Canadian Institutes of Health Research (CIHR, MOP‐68938) and Heart and Stroke Foundation of Canada to L. Wu.)