Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells.

J C Tsai; H Wang; M A Perrella; M Yoshizumi; N E Sibinga; L C Tan; E Haber; T H Chang; R Schlegel; M E Lee

doi:10.1172/JCI118383

Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

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Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

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Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

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Published in Volume 97, Issue 1 on January 1, 1996
J Clin Invest. 1996;97(1):146–153. https://doi.org/10.1172/JCI118383.
© 1996 The American Society for Clinical Investigation

Published January 1, 1996 - Version history

Homocysteine is an important and independent risk factor for arteriosclerosis. We showed previously that homocysteine stimulates vascular smooth muscle cell proliferation, a hallmark of arteriosclerosis. We show here that homocysteine and serum increased DNA synthesis synergistically in both human and rat aortic smooth muscle cells (RASMCs). Treatment of quiescent RASMCs with 1 mM homocysteine or 2% calf serum for 36 h increased cyclin A mRNA levels by 8- and 14-fold, respectively, whereas homocysteine plus serum increased cyclin A mRNA levels by 40-fold, indicating a synergistic induction of cyclin A mRNA. Homocysteine did not increase the half-life of cyclin A mRNA (2.9 h), but it did increase the transcriptional rate of the cyclin A gene in nuclear run-on experiments. The positive effect of homocysteine on cyclin A gene transcription was confirmed by our finding that homocysteine increased cyclin A promoter activity and ATF-binding protein levels in RASMCs. Finally, 1 mM homocysteine increased cyclin A protein levels and cyclin A-associated kinase activity by threefold. This homocysteine-induced expression lesions by promoting proliferation of vascular smooth muscle cells.

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Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells.

J C Tsai, H Wang, M A Perrella, M Yoshizumi, N E Sibinga, L C Tan, E Haber, T H Chang, R Schlegel, and M E Lee

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Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells.

J C Tsai, H Wang, M A Perrella, M Yoshizumi, N E Sibinga, L C Tan, E Haber, T H Chang, R Schlegel, and M E Lee

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