PMID- 16226235
OWN - NLM
STAT- MEDLINE
DCOM- 20060503
LR  - 20220311
IS  - 0008-6363 (Print)
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 69
IP  - 1
DP  - 2006 Jan
TI  - Hyperhomocysteinemia inhibits post-injury reendothelialization in mice.
PG  - 253-62
AB  - OBJECTIVE: Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular 
      disease and has been reported to inhibit endothelial cell (EC) growth. 
      Notwithstanding, precisely how HHcy regulates EC growth in vivo remains unknown. 
      In this study, we established a mouse model of endothelial injury and 
      reendothelialization and examined the role and mechanism of HHcy in endothelial 
      repair. METHODS AND RESULTS: A mouse model of carotid artery air-dry endothelium 
      denudation and reendothelialization was established and used to evaluate 
      post-injury endothelial repair in mice with the gene deletion of 
      cystathionine-beta-synthase (CBS). Moderate and severe HHcy were induced in 
      CBS+/+ and CBS-/+ mice through a high-methionine diet. Post-injury 
      reendothelialization, which correlated with increased post-injury neointima 
      formation, was impaired in severe HHcy mice. To elucidate the underlying 
      mechanism, we examined circulating endothelial progenitor cells (EPC) in HHcy 
      mice and studied the effect of homocysteine (Hcy) on proliferation, migration, 
      and adhesion of human umbilical vein endothelial cells (HUVEC). The peripheral 
      EPC population was not significantly altered in HHcy mice. Hcy had a profound 
      inhibitory effect on EC proliferation and migration at physiologically relevant 
      concentrations and inhibited EC adhesion at concentrations of 200 microM and 
      higher. CONCLUSION: We have established a convenient and accurate mouse model of 
      carotid injury in which the reendothelialization process can be precisely 
      quantified. In addition, we have observed impaired reendothelialization and 
      increased neointimal formation in severe HHcy mice. The capacity of Hcy to 
      inhibit proliferation and migration of EC may be responsible for impaired 
      reendothelialization and contribute to arteriosclerosis in HHcy.
FAU - Tan, Hongmei
AU  - Tan H
AD  - Department of Medicine, Baylor College of Medicine, USA.
FAU - Jiang, Xiaohua
AU  - Jiang X
FAU - Yang, Fan
AU  - Yang F
FAU - Li, Zhaohui
AU  - Li Z
FAU - Liao, Dan
AU  - Liao D
FAU - Trial, JoAnn
AU  - Trial J
FAU - Magera, Mark J
AU  - Magera MJ
FAU - Durante, William
AU  - Durante W
FAU - Yang, Xiaofeng
AU  - Yang X
FAU - Wang, Hong
AU  - Wang H
LA  - eng
GR  - K02 HL074925/HL/NHLBI NIH HHS/United States
GR  - HL74925/HL/NHLBI NIH HHS/United States
GR  - HL59976/HL/NHLBI NIH HHS/United States
GR  - R01 HL077288/HL/NHLBI NIH HHS/United States
GR  - HL77288/HL/NHLBI NIH HHS/United States
GR  - HL67033/HL/NHLBI NIH HHS/United States
GR  - HL36045/HL/NHLBI NIH HHS/United States
GR  - R01 HL036045/HL/NHLBI NIH HHS/United States
GR  - R01 HL059976/HL/NHLBI NIH HHS/United States
GR  - R01 HL067033/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051013
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Carotid Artery Injuries/*metabolism/pathology
MH  - Cell Adhesion/drug effects
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Cystathionine beta-Synthase/genetics
MH  - Endothelial Cells/drug effects/*metabolism/pathology
MH  - Endothelium, Vascular/*injuries/metabolism
MH  - Homocysteine/pharmacology
MH  - Humans
MH  - Hyperhomocysteinemia/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Regeneration
MH  - Stem Cells/pathology
MH  - Tunica Intima/pathology
MH  - Umbilical Veins/cytology
MH  - *Wound Healing
PMC - PMC4400842
MID - NIHMS677890
EDAT- 2005/10/18 09:00
MHDA- 2006/05/04 09:00
PMCR- 2015/04/17
CRDT- 2005/10/18 09:00
PHST- 2005/03/23 00:00 [received]
PHST- 2005/08/26 00:00 [revised]
PHST- 2005/08/29 00:00 [accepted]
PHST- 2005/10/18 09:00 [pubmed]
PHST- 2006/05/04 09:00 [medline]
PHST- 2005/10/18 09:00 [entrez]
PHST- 2015/04/17 00:00 [pmc-release]
AID - S0008-6363(05)00431-1 [pii]
AID - 10.1016/j.cardiores.2005.08.016 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2006 Jan;69(1):253-62. doi: 10.1016/j.cardiores.2005.08.016. Epub 
      2005 Oct 13.