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© 2007 American Society for Nutrition J. Nutr. 137:1895-1900, August 2007


Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Dietary Iron Deficiency Compromises Normal Development of Elastic Fibers in the Aorta and Lungs of Chicks1–3,

Charles H. Hill4, Chris M. Ashwell5, Shelly J. Nolin4, Fred Keeley5, Catherine Billingham5, Aleksander Hinek5 and Barry Starcher6,*

4 Department of Poultry Science, North Carolina State University, Raleigh, NC 27695; 5 Division of Cardiovascular Research and Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Canada M5G 1X8; and 6 Department of Biochemistry and University of Texas Health Center, University of Texas, Tyler, TX 75708

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

Elastic fibers play a key role in the structure and function of numerous organs that require elasticity. Elastogenesis is a complex process in which cells first produce a microfibrillar scaffold, composed of numerous structural proteins, upon which tropoelastin assembles to be cross-linked into polymeric elastin. Recently, it was demonstrated that low concentrations of free iron upregulate elastin gene expression in cultured fibroblasts. The present studies were conducted to assess whether low-iron diets would affect the deposition of elastic fibers in an in vivo model. One-day-old chicks were fed semipurified diets containing 1.3 (low), 12 (moderate), and 24 (control) mg/kg of iron. After 3 wk, chicks in the low-iron group were underweight and anemic. Their aortas were smaller with significantly thinner walls than control chicks, yet elastin or collagen content did not decrease relative to total protein. They also demonstrated a significantly lower stress-strain resistance than the controls. Electron microscopy demonstrated that aortic and lung smooth muscle cells were vacuolated and surrounded by loose extracellular matrix and disorganized elastic lamellae with diffuse and fragmented networks of elastic fibers and microfibrils. Immunohistology demonstrated that fibrillin-3 (FBN3) was disorganized and markedly reduced in amount in aortas of the low-iron chicks. Elastin messenger RNA levels were not downregulated in the tissues from the low-iron-fed chicks; however, there was a significant reduction in expression of the FBN1 and FBN3 genes compared with control chicks. The studies indicate that iron deficiency had a pronounced negative effect on elastic fiber development and suggests that fibrillin may have an important role in this pathology.








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