Affiliations: Department of Biochemistry, Faculty of Medicine,
Marmara University, 34668 Haydarpasa, Istanbul, Turkey | Institute of Biochemistry and Molecular Biology,
University of Bern, 3012 Bern, Switzerland
Note: [] Address for correspondence: Prof. Nesrin Kartal Özer,
Department of Biochemistry, Faculty of Medicine, Marmara University, Haydarpasa
34668 Istanbul, Turkey. Tel.: +90 216 414 47 33; Fax: +90 216 418 10 47;
E-mail: nkozer@marmara.edu.tr
Abstract: Hyperhomocysteinemia has been identified as an important and
independent risk factor for cerebral, coronary and peripheral atherosclerosis.
However the mechanisms by which homocysteine promote atherosclerotic plaque
formation are not clearly defined. Earlier reports have suggested that
homocysteine exert its effect via the
H_2O_2 produced during its metabolism. To
evaluate which signalling molecules are involved in homocysteine induced
atherosclerotic changes during the pathogenesis of vascular diseases, we
examined homocysteine induced smooth muscle cell proliferation in the presence
of different signal transduction inhibitors. We show that MAPK kinase pathway
is involved in homocysteine induced DNA synthesis and proliferation of vascular
smooth muscle cells in the presence of the peroxide scavenging enzyme,
catalase. Our data suggest that homocysteine induces smooth muscle cell growth
through a pathway that is independent of
H_2O_2, that involves MAPK kinase
activation, and that results in accelerated atherosclerosis.
Keywords: Homocysteine, atherosclerosis, signal transduction, smooth muscle cells
Journal: BioFactors, vol. 24, no. 1-4, pp. 193-199, 2005
