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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Tate, Jillian R. / Tsongalis, Gregory J.

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Hyperhomocysteinemia, DNA methylation and vascular disease

Md S. Jamaluddin1 / Xiaofeng Yang2 / Hong Wang3

1Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA

2Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA

3Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA

Corresponding author: Hong Wang, Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USA Phone: +1-215-707-5986, Fax: +1-215-707-7068,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 45, Issue 12, Pages 1660–1666, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: 10.1515/CCLM.2007.350, December 2007

Publication History

Published Online:


Hyperhomocysteinemia (HHcy) has been established as a potent independent risk factor for cardiovascular disease (CVD) and the underlying mechanism is largely unknown. We were the first to propose that hypomethylation is the key biochemical mechanism by which homocysteine (Hcy) inhibits endothelial cell (EC) growth. We reported that clinically relevant concentrations of Hcy (10–50 μmol/L) exerts highly selective inhibitory effects on cyclin A transcription and EC growth through a hypomethylation related mechanism, which blocks cell cycle progression and endothelium regeneration. Recently, we demonstrated that Hcy reduces DNA methyltransferase 1 (DNMT1) activity and demethylates cyclin A promoter leading to cyclin A chromatin remodeling. We found that adenovirus-transduced DNMT1 gene expression reverses the inhibitory effect of Hcy on cyclin A expression and EC growth inhibition. We hypothesize that DNA hypomethylation is a key biochemical mechanism responsible for Hcy-induced cyclin A suppression and growth inhibition in EC and contributes to CVD.

Clin Chem Lab Med 2007;45:1660–6.

Keywords: atherosclerosis; cardiovascular disease; chromatin remodeling; DNA methylation; endothelial cell growth; homocysteine

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