Published online before print January 19, 2006, doi: 10.1161/01.ATV.0000204408.01416.16
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 American Heart Association, Inc.
Vascular Biology |
Influence of Folate on Arterial Permeability and Stiffness in the Absence or Presence of Hyperhomocysteinemia
From the College of Health (J.D.S.), University of Utah, Salt Lake City, Utah; the Division of Endocrinology (U.B.Z., C.N.A., A.E.M., J.C.R.), Clinical Nutrition, and Vascular Medicine, University of California, Davis, Calif; and the Department of Internal Medicine (S.R.L.), University of Iowa College of Medicine and Cardiovascular Center, VA Medical Center, Iowa City, Iowa.
Correspondence to J. David Symons, PhD, University of Utah School of Medicine, Building 585, Rm 152.30 N 2030 E, Salt Lake City, UT 84132. E-mail j.david.symons{at}hsc.utah.edu
Objective— Elevated plasma total homocysteine (tHcy) is associated with risk for cardiovascular disease. A common cause of mild hyperhomocysteinemia (HHcy) is folate deficiency. We sought to determine whether folate deficiency per se increases arterial permeability (quantitative fluorescence microscopy) and stiffness (vessel elastigraph), and whether the effects of folate deficiency are more severe in the presence of mild HHcy.
Methods and Results— Heterozygous cystathionine ß-synthase (CBS)-deficient mice (CBS+/–) and their wild-type littermates (CBS+/+) were fed chow containing either standard (Con) or relatively low amounts of folate (LF) for 18±3 weeks. Liver folate (µg folate/g liver) and tHcy (µM), respectively, were 12±1 and 8±1 in CBS+/+ Con mice (n=12), and 8±1 and 8±1 in CBS+/+ LF animals (n=5). Carotid arterial permeability was &38% greater (P<0.05) in CBS+/+ LF versus Con mice, but vascular stiffening was unaltered. Liver folate and tHcy, respectively, were 13±1 and 11±1 in CBS+/– Con mice (n=16), and 8±1 and 16±3 in CBS+/– LF animals (n=6). Carotid arterial dextran accumulation was &31% greater, and maximal strain in aortae was &20% lower (both P<0.05) in CBS+/– LF versus Con mice.
Conclusion— Taken together, low folate (P<0.05) combined with mild HHcy (P<0.05) in CBS+/– mice produced more arterial dysfunction compared with low folate alone (ie, CBS+/+ mice). These findings may be particularly relevant to elderly individuals because tHcy and deficiencies of folate metabolism increase with age.
We determined the influence of low-folate per se in the absence and presence of mild hyperhomocysteinemia (HHcy) on arterial permeability and stiffness. Arterial permeability was &38% greater (P<0.05) but vascular stiffening was unaltered by low folate per se. In the combined presence of low-folate and HHcy, vascular permeability (&31%) and stiffness (&20%) were greater (P<0.05).
Key Words: mice • cystathionine ß-synthase • carotid artery • aorta • cardiovascular risk factors
This article has been cited by other articles:
 |
|
 |
|
  P. N Baker, S. J Wheeler, T. A Sanders, J. E Thomas, C. J Hutchinson, K. Clarke, J. L Berry, R. L Jones, P. T Seed, and L. Poston A prospective study of micronutrient status in adolescent pregnancy Am. J. Clinical Nutrition, April 1, 2009; 89(4): 1114 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dayal and S. R. Lentz Murine Models of Hyperhomocysteinemia and Their Vascular Phenotypes Arterioscler Thromb Vasc Biol, September 1, 2008; 28(9): 1596 - 1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Mullick, U. B. Zaid, C. N. Athanassious, S. R. Lentz, J. C. Rutledge, and J. D. Symons Hyperhomocysteinemia increases arterial permeability and stiffness in mice Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1349 - R1354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dayal, K. M. Wilson, L. Leo, E. Arning, T. Bottiglieri, and S. R. Lentz Enhanced susceptibility to arterial thrombosis in a murine model of hyperhomocysteinemia Blood, October 1, 2006; 108(7): 2237 - 2243. [Abstract] [Full Text] [PDF]
|
|