This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lubec, B. Articles by Gialamas, J. Search for Related Content PubMed PubMed Citation Articles by Lubec, B. Articles by Gialamas, J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(Circulation. 1996;94:2620-2625.)
© 1996 American Heart Association, Inc.

Articles

Homocysteine Increases Cyclin-Dependent Kinase in Aortic Rat Tissue

Barbara Lubec, MD; Olga Labudova, PhD; Harald Hoeger, PhD; Adolf Muehl, PhD; Susanne Fang-Kircher, MD; Manfred Marx, MD; Wilhelm Mosgoeller, MD; J. Gialamas, PhD

the University of Vienna (Austria), Department of Pediatrics, Division of Neonatology (B.L.); the Institute of Animal Breeding (H.H., J.G.); the Institute of Histology (W.M.); the Institute of Medicinal Chemistry (S.F.-K.); and the Department of Pediatrics, Division of Cardiology (O.L., M.M., A.M.), Vienna, Austria.

Correspondence to Dr Barbara Lubec, University of Vienna, Department of Pediatrics, Division of Neonatology, Waehringer Guertel l8, A lo9o Vienna, Austria.

Background Hyperhomocyst(e)inemia is strongly associated with occlusive arterial disease. A direct effect of homocysteine on the proliferation of smooth muscle cells was proposed recently. This observation led us to examine the effect of homocysteine on cyclin-dependent kinase, the starter of mitosis and reflecting proliferation.

Methods and Results Seventy Him:OFA rats were divided into seven groups. For 12 weeks, 10 rats were fed homocysteine 25 mg/kg body weight per day, 10 were fed 50 mg/kg body wt per day, and 10 were fed 100 mg/kg body weight per day; 10 were given homocysteic acid 100 mg/kg body weight per day, 10 were administered cysteine 100 mg/kg body weight per day, and 10 were given ascorbic acid 270 mg/kg body weight per day. Ten remained untreated and served as controls. Aortic cyclin-dependent kinase was determined at the transcriptional (mRNA) and protein levels. Phosphokinase C and aortic homocyst(e)ine also were evaluated in aortic tissue. Aortic cyclin-dependent kinase protein was significantly (P=.0001) elevated in the three homocysteine-treated groups, and mRNA cyclin-dependent kinase levels were significantly elevated in the rats given the 50 and 100 mg/kg body weight per day protocol. Endothelial damage was shown at higher homocysteine doses as reflected by circulating ACE and von Willebrand factor changes. Proliferation of cells of the aortic wall by bromodeoxyuridine incorporation could be shown in the high-dose homocysteine group only.

Conclusions Our findings indicate that homocysteine specifically stimulates aortic cyclin-dependent kinase at the transcriptional level, with the possible consequence of proliferation of aortic cells as revealed by incorporation of bromodeoxyuridine in the aortic wall.

Key Words: homocysteine • cyclin-dependent kinase • proliferation

This article has been cited by other articles:

				Z. Ungvari, A. Csiszar, J. G. Edwards, P. M. Kaminski, M. S. Wolin, G. Kaley, and A. Koller Increased Superoxide Production in Coronary Arteries in Hyperhomocysteinemia: Role of Tumor Necrosis Factor-{alpha}, NAD(P)H Oxidase, and Inducible Nitric Oxide Synthase Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 418 - 424. [Abstract] [Full Text] [PDF]

				A. De Bree, W. M. M. Verschuren, D. Kromhout, L. A. J. Kluijtmans, and H. J. Blom Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease Pharmacol. Rev., December 1, 2002; 54(4): 599 - 618. [Abstract] [Full Text] [PDF]

				J. Zhou, J. Moller, C. C. Danielsen, J. Bentzon, H. B. Ravn, R. C. Austin, and E. Falk Dietary Supplementation With Methionine and Homocysteine Promotes Early Atherosclerosis but Not Plaque Rupture in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, September 1, 2001; 21(9): 1470 - 1476. [Abstract] [Full Text] [PDF]

				C. W. Compher, B. P. Kinosian, N. Evans-Stoner, J. Huzinec, and G. P. Buzby Hyperhomocysteinemia Is Associated with Venous Thrombosis in Patients with Short Bowel Syndrome JPEN J Parenter Enteral Nutr, January 1, 2001; 25(1): 1 - 8. [Abstract] [PDF]

				J Thambyrajah and J.N Townend Homocysteine and atherothrombosis--mechanisms for injury Eur. Heart J., June 2, 2000; 21(12): 967 - 974. [PDF]

				V. Fonseca, S. C. Guba, and L. M. Fink Hyperhomocysteinemia and the Endocrine System: Implications for Atherosclerosis and Thrombosis Endocr. Rev., October 1, 1999; 20(5): 738 - 759. [Abstract] [Full Text]

				J. Y. Jeremy, D. Rowe, A. M. Emsley, and A. C. Newby Nitric oxide and the proliferation of vascular smooth muscle cells Cardiovasc Res, August 15, 1999; 43(3): 580 - 594. [Full Text] [PDF]

				J.-M. Li and G. Brooks Cell cycle regulatory molecules (cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors) and the cardiovascular system; potential targets for therapy? Eur. Heart J., March 2, 1999; 20(6): 406 - 420. [PDF]