PMID- 16793933
OWN - NLM
STAT- MEDLINE
DCOM- 20061129
LR  - 20200930
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 291
IP  - 5
DP  - 2006 Nov
TI  - Hyperhomocysteinemia increases arterial permeability and stiffness in mice.
PG  - R1349-54
AB  - 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.
FAU - Mullick, Adam E
AU  - Mullick AE
AD  - 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).
FAU - Zaid, Ussama B
AU  - Zaid UB
FAU - Athanassious, Christian N
AU  - Athanassious CN
FAU - Lentz, Steven R
AU  - Lentz SR
FAU - Rutledge, John C
AU  - Rutledge JC
FAU - Symons, J David
AU  - Symons JD
LA  - eng
GR  - DK-35747/DK/NIDDK NIH HHS/United States
GR  - HL-55667/HL/NHLBI NIH HHS/United States
GR  - HL-63943/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 - 20060622
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Lipoproteins)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11062-77-4 (Superoxides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Arteries/physiology
MH  - Atherosclerosis/etiology/pathology/*physiopathology
MH  - Capillary Permeability/*physiology
MH  - Elasticity
MH  - Endothelium, Vascular/metabolism/pathology/physiopathology
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/*physiopathology
MH  - Lipoproteins/metabolism
MH  - Methionine/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/metabolism
MH  - Superoxides/metabolism
MH  - Vascular Resistance/physiology
EDAT- 2006/06/24 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/06/24 09:00
PHST- 2006/06/24 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/06/24 09:00 [entrez]
AID - 00335.2006 [pii]
AID - 10.1152/ajpregu.00335.2006 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1349-54. doi: 
      10.1152/ajpregu.00335.2006. Epub 2006 Jun 22.