Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-10-9
pubmed:abstractText
We have reported that hyperhomocysteinemia (HHcy) evoked by folate depletion increases arterial permeability and stiffness in rats and that low folate without HHcy increases arterial permeability in mice. In this study, we hypothesized that HHcy independently increases arterial permeability and stiffness in mice. C57BL/6J mice that received rodent chow and water [control (Con), n=12] or water supplemented with 0.5% L-methionine (HHcy, n=12) for 18+/-3 wk had plasma homocysteine concentrations of 8+/-1 and 41+/-1 microM, respectively (P<0.05), and similar liver folate (approximately 12+/-2 microg folate/g liver). Carotid arterial permeability, assessed as dextran accumulation using quantitative fluorescence microscopy, was greater in HHcy (3.95+/-0.4 ng.min-1.cm-2) versus Con (2.87+/-0.41 ng.min-1.cm-2) mice (P<0.05). Stress versus strain curves generated using an elastigraph indicated that 1) maximal stress (N/mm2), 2) physiological stiffness (low-strain Young's modulus, mN/mm), and 3) maximal stiffness (high-strain Young's modulus, N/mm) were higher (P<0.05) in aortas from HHcy versus Con mice. Thus, chronic HHcy increases arterial permeability and stiffness. Carotid arterial permeability also was assessed in age-matched C57BL/6J mice before and after incubation with 1) xanthine (0.4 mg/ml)/xanthine oxidase (0.2 mg/ml; X/XO) to generate superoxide anion (O2-) or 50 microM DL-homocysteine in the presence of 2) vehicle, 3) 300 microM diethylamine-NONOate (DEANO; a nitric oxide donor), or 4) 10(-3) M 4,5-dihydroxy-1,3-benzene disulfonic acid (tiron; a nonenzymatic intracellular O2- scavenger). Compared with preincubation values, X/XO and dl-homocysteine increased (P<0.05) permeability by 66+/-11% and 123+/-8%, respectively. DL-Homocysteine-induced increases in dextran accumulation were blunted (P<0.05) by simultaneous incubation with DEANO or tiron. Thus, acute HHcy increases arterial permeability by generating O2- to an extent whereby nitric oxide bioavailability is reduced.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0363-6119
pubmed:author
pubmed:issnType
Print
pubmed:volume
291
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R1349-54
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Hyperhomocysteinemia increases arterial permeability and stiffness in mice.
pubmed:affiliation
Univ. of Utah School of Medicine, Bldg. 585, Rm. 152, 30 N 2030 E, Salt Lake City, UT 84132 (e-mail j.david.symons@hsc.utah.edu).
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural