PMID- 16424349 OWN - NLM STAT- MEDLINE DCOM- 20060714 LR - 20141120 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 26 IP - 4 DP - 2006 Apr TI - Influence of folate on arterial permeability and stiffness in the absence or presence of hyperhomocysteinemia. PG - 814-8 AB - 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 beta-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 (microg folate/g liver) and tHcy (microM), 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. CONCLUSIONS: 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. FAU - Symons, J David AU - Symons JD AD - College of Health, University of Utah, Salt Lake City, Utah, USA. j.david.symons@hsc.utah.edu FAU - Zaid, Ussama B AU - Zaid UB FAU - Athanassious, Christian N AU - Athanassious CN FAU - Mullick, Adam E AU - Mullick AE FAU - Lentz, Steven R AU - Lentz SR FAU - Rutledge, John C AU - Rutledge JC LA - eng GR - 35747/PHS HHS/United States GR - HL55667/HL/NHLBI NIH HHS/United States GR - HL63943/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20060119 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 935E97BOY8 (Folic Acid) RN - EC 4.2.1.22 (Cystathionine beta-Synthase) SB - IM MH - Animals MH - Capillary Permeability/*drug effects MH - Carotid Arteries/drug effects/*metabolism/physiopathology MH - Cystathionine beta-Synthase/*biosynthesis/deficiency MH - Endothelium, Vascular/metabolism/physiopathology MH - Folic Acid/*administration & dosage/blood/pharmacokinetics MH - Humans MH - Hyperhomocysteinemia/blood/drug therapy/physiopathology MH - In Vitro Techniques MH - Mice MH - Vasoconstriction/drug effects EDAT- 2006/01/21 09:00 MHDA- 2006/07/15 09:00 CRDT- 2006/01/21 09:00 PHST- 2006/01/21 09:00 [pubmed] PHST- 2006/07/15 09:00 [medline] PHST- 2006/01/21 09:00 [entrez] AID - 01.ATV.0000204408.01416.16 [pii] AID - 10.1161/01.ATV.0000204408.01416.16 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):814-8. doi: 10.1161/01.ATV.0000204408.01416.16. Epub 2006 Jan 19.