QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An erratum has been published 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 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 Google Scholar Google Scholar Articles by Hill, C. H. Articles by Starcher, B. Search for Related Content PubMed PubMed Citation Articles by Hill, C. H. Articles by Starcher, B.

---

Biochemical and Molecular Actions of Nutrients

Fibrillin-2 Defects Impair Elastic Fiber Assembly in a Homocysteinemic Chick Model

Charles H. Hill, Robert Mecham^* and Barry Starcher¹

Department of Poultry Science, North Carolina State University, Raleigh, NC; ^* Department of Cell Biology and Physiology, Washington University Medical Center, St. Louis, MO and Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, TX

¹To whom correspondence should be addressed. E-mail: barry.starcher{at}uthct.edu.

Homocysteinemia in humans is associated with vascular complications that increase the risk for atherosclerosis and stroke. Animal studies have shown that the disease is multifactorial and includes lesions associated with the elastin component of the extracellular matrix. In the following experiments we have used the aortas from rapidly growing chicks to assess the cause of the elastin defects resulting from homocysteinemia. Day-old chicks were fed diets containing varying amounts of DL-methionine, DL-homocysteine, homocysteine thiolactone or DL-cysteine for periods up to 9 wk. Three weeks after feeding 2% DL-methionine the plasma methionine was elevated > 20-fold, whereas plasma homocysteine was more than 3-fold normal plasma values. The aortas showed severe histopathology, evidenced by the pronounced separation of elastic lamellae with marked smooth muscle proliferation and, in some instances, aneurysms. There was no evidence of decreased desmosine content or a significant reduction in lysyl oxidase in the aortas from the treated groups compared to those from controls. Increasing other dietary factors such as the vitamins required for methionine metabolism had no effect on the development of the vascular lesions. Twenty to 30% of the chicks fed the high methionine diets exhibited severe neurological problems, expressed as tonic contractions or seizures. Electron microscopy revealed disordered aortic elastic fibrils, associated with either an absence of or disrupted assembly of microfibrils. Immunohistochemical studies demonstrated a loss of fibrillin-2 immunoreactivity in the aortas of chicks fed 2% methionine. The studies suggest that elevated plasma methionine or its metabolites disrupt normal microfibril configuration, leading to the assembly of aberrant elastic fibers.

KEY WORDS: • microfibrils • homocysteinemia • elastin • fibrillin • desmosine

This article has been cited by other articles:

				G. I. Stangl, K. Weisse, C. Dinger, F. Hirche, C. Brandsch, and K. Eder Homocysteine Thiolactone-Induced Hyperhomocysteinemia Does Not Alter Concentrations of Cholesterol and SREBP-2 Target Gene mRNAs in Rats Experimental Biology and Medicine, January 1, 2007; 232(1): 81 - 87. [Abstract] [Full Text] [PDF]

				M. Herrmann, T. Widmann, G. Colaianni, S. Colucci, A. Zallone, and W. Herrmann Increased Osteoclast Activity in the Presence of Increased Homocysteine Concentrations Clin. Chem., December 1, 2005; 51(12): 2348 - 2353. [Abstract] [Full Text] [PDF]

				D. Hubmacher, K. Tiedemann, R. Bartels, J. Brinckmann, T. Vollbrandt, B. Batge, H. Notbohm, and D. P. Reinhardt Modification of the Structure and Function of Fibrillin-1 by Homocysteine Suggests a Potential Pathogenetic Mechanism in Homocystinuria J. Biol. Chem., October 14, 2005; 280(41): 34946 - 34955. [Abstract] [Full Text] [PDF]