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Letters to the Editor

Reply to Drs. Wagner and Koury

School of Public Health
Sun Yat-sen University
Guangzhou, 510080 PR-China

^* To whom correspondence should be addressed. E-mail: lingwh{at}mail.sysu.edu.cn.

Dear Editor,

We have read the letter from Wagner and Koury (1) concerning our article. We appreciate their concerns and provide our reply to their comments.

First, to determine S-adenosylhomocysteine (AdoHcy or SAH) in mouse plasma, we modified the method of Frantzen et al. (2) that was used to measure homocysteine (Hcy). Although S-adenosylmethionine (AdoMet or SAM) showed a cross-reactivity in concentrations >10µmol/L in the article by Frantzen et al., this is 50–100 times greater than the concentration usually found in human plasma. We eliminated the procedure involving the enzymatic conversion of Hcy to AdoHcy and modified the conditions of constructing the calibration curve (3). To eliminate cross-reaction of the anti-AdoHcy antibody with interfering compounds in plasma, including plasma AdoMet, we prepared the standards for calibration by adding AdoHcy into the control plasma and subjected these controls to the same pretreatment deproteinization procedures as the unknown samples to construct a calibration curve. Another study of hyperhomocysteinemic patients with occlusive vascular disease, by Loehrer et al. (4), showed that a reduced ratio of AdoMet:AdoHcy in both plasma and erythrocytes was due to elevated AdoHcy levels. In kidney failure patients with hyperhomocysteinemia, Perna et al. (5,6) found a 4- to 8-fold increase in intracellular AdoHcy, minimal change in AdoMet. For these reasons, we think that the method reported in our article is suitable to measure the changes of plasma AdoHcy of mice fed diets varying in methionine and B vitamins.

Second, Kerins et al. (7) reported that AdoHcy was elevated in cardiovascular disease in a population with extensive atherosclerosis. However, the authors in this case investigated an epidemiological phenomenon, and concluded that plasma AdoHcy appears to be a more sensitive indicator of cardiovascular disease than plasma homocysteine. Our results do not support Hcy as an independent risk factor of atherosclerosis. Furthermore, we confirmed, to our knowledge for the first time, that plasma AdoHcy is a better biomarker of atherosclerosis than Hcy in a mouse model by analyzing the correlation between plaque areas and plasma AdoHcy, Hcy concentrations, which seems to be much stronger evidence supporting the concept. We also provided evidence that negative correlations exist between plasma AdoHcy concentration and both DNA methyltransferase activity and global DNA methylation status in the aortic tissue during the development of atherosclerosis in the same mouse model. This suggests that the inhibitory effects of AdoHcy on the methyltransferases may potentially be an important pathogenic mechanism in the development of atherosclerosis.

Manuscript received 20 February 2008.

	LITERATURE CITED

TOP LITERATURE CITED

 

1. Wagner C, Koury MJ. Plasma S-adenosylhomocysteine versus homocysteine as a marker for vascular disease. J Nutr. 2008;138:980.[Free Full Text]

2. Frantzen F, Faaren AL, Alfheim I, Nordhei AK. Enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clin Chem. 1998;44:311–6.[Abstract/Free Full Text]

3. Liu C, Wang Q, Guo HH, Xia M, Yuan Q, Hu Y, Zhu HL, Hou MJ, Ma J, et al. Plasma S-adenosylhomocysteine is a better biomarker of atherosclerosis than homocysteine in apolipoprotein e-deficient mice fed high dietary methionine. J Nutr. 2008;138:311–5.[Abstract/Free Full Text]

4. Loehrer FM, Tschopl M, Angst CP, Litynski P, Jager K, Fowler B, Haefeli WE. Disturbed ratio of erythrocyte and plasma S-adenosylmethionine/S- adenosylhomocysteine in peripheral arterial occlusive disease. Atherosclerosis. 2001;154:147–54.[Medline]

5. Perna AF, Ingrosso D, De Santo NG, Galletti P, Brunone M, Zappia V. Metabolic consequences of folate-induced reduction of hyperhomocysteinemia in uremia. J Am Soc Nephrol. 1997;8:1899–905.[Abstract]

6. Perna AF, Castaldo P, De Santo NG, di Carlo E, Cimmino A, Gillti P, Zappia V, Ingrosso D. Plasma proteins containing damaged L-aspartyl residues are increased in uremia: implications for mechanism. Kidney Int. 2001;59:2299–308.[Medline]

7. Kerins DM, Koury MJ, Capdevila A, Rana S, Wagner C. Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine. Am J Clin Nutr. 2001;74:723–9.[Abstract/Free Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Liu, C. Articles by Ling, W. Search for Related Content PubMed Articles by Liu, C. Articles by Ling, W.