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This Article Full Text Full Text (PDF) 077859.Supplemental Data All Versions of this Article: clinchem.2006.077859v1 53/4/773    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Herrmann, M. Articles by Herrmann, W. Search for Related Content PubMed PubMed Citation Articles by Herrmann, M. Articles by Herrmann, W. Related Collections Other Areas of Clinical Chemistry Proteomics and Protein Markers

Hyperhomocysteinemia and Myocardial Expression of Brain Natriuretic Peptide in Rats

Departments of¹ Clinical Chemistry and Laboratory Medicine and ² Department of Internal Medicine III, University Hospital of Saarland, Homburg/Saar, Germany.
³ Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
⁴ Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany.

^aAddress correspondence to this author at: Wolfgang Herrmann, Abteilung für Klinische Chemie und Laboratoriumsmedizin / Zentrallabor, Universitätsklinikum des Saarland, D-66421 Homburg/Saar, Germany. Fax +496841 1630703, E-mail kchwher{at}uniklinik-saarland.de.

Background: Hyperhomocysteinemia (HHcy) has been linked to impaired left ventricular function and clinical class in patients with chronic heart failure. We hypothesized that HHcy stimulates myocardial brain natriuretic peptide (BNP) expression and induces adverse left ventricular remodeling.

Methods: We randomized 50 rats into 5 groups. Groups Co1 and Co2 (controls) received a typical diet. Groups Meth, Hcy1, and Hcy2 were fed the same diet supplemented with 2.4% methionine, 1% homocystine, and 2% homocystine, respectively. After 12 weeks, we measured total plasma homocysteine (tHcy) and BNP in plasma and tissue, and we performed histomorphometric analyses.

Results: All animals had comparable baseline body weight [mean (SD) 234 (26) g] and total circulating Hcy [4.7 (1.7) µmol/L]. After 12 weeks of treatment, total circulating Hcy increased in Meth, Hcy1, and Hcy2 [27.3 (8.8), 40.6 (7.0), and 54.0 (46.0) µmol/L, respectively] and remained unchanged in Co1 and Co2. Serum BNP significantly increased in 1 of 10 animals in Meth, 3 of 10 animals in Hcy1, and 3 of 10 animals in Hcy2. Median (25th–75th percentile) BNP tissue concentrations in Hcy1 and Hcy2 were 55% higher than in the corresponding controls [Co1 vs Hcy1, 225 (186–263) vs 338 (262–410) pg/mg protein, P = 0.05; Co2 vs Hcy2, 179 (107–261) vs 308 (192–429) pg/mg protein, P = 0.12]. In the Meth group, BNP expression was comparable to that of controls [200 (159–235) vs 225 (186–263) pg/mg protein, P = 0.32]. The percentage of perivascular and interstitial collagen and mast cell infiltration were comparable in all groups, indicating no adverse cardiac remodeling.

Conclusion: Three months of intermediate HHcy stimulated increased cardiac BNP expression that was not accompanied by adverse cardiac remodeling.

The following articles in journals at HighWire Press have cited this article:

				M. Shimano, Y. Inden, Y. Tsuji, H. Kamiya, T. Uchikawa, R. Shibata, and T. Murohara Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation Europace, August 1, 2008; 10(8): 961 - 966. [Abstract] [Full Text] [PDF]