PMID- 18371555
OWN - NLM
STAT- MEDLINE
DCOM- 20080429
LR  - 20220408
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 51
IP  - 13
DP  - 2008 Apr 1
TI  - Hypoxia, hypoxia-inducible transcription factor, and macrophages in human 
      atherosclerotic plaques are correlated with intraplaque angiogenesis.
PG  - 1258-65
LID - 10.1016/j.jacc.2007.12.025 [doi]
AB  - OBJECTIVES: We sought to examine the presence of hypoxia in human carotid 
      atherosclerosis and its association with hypoxia-inducible transcription factor 
      (HIF) and intraplaque angiogenesis. BACKGROUND: Atherosclerotic plaques develop 
      intraplaque angiogenesis, which is a typical feature of hypoxic tissue and 
      expression of HIF. METHODS: To examine the presence of hypoxia in atherosclerotic 
      plaques, the hypoxia marker pimonidazole was infused before carotid 
      endarterectomy in 7 symptomatic patients. Also, the messenger ribonucleic acid 
      (mRNA) and protein expression of HIF1 alpha, HIF2 alpha, HIF-responsive genes 
      (vascular endothelial growth factor [VEGF], glucose transporter [GLUT]1, GLUT3, 
      hexokinase [HK]1, and HK2), and microvessel density were determined in a larger 
      series of nondiseased and atherosclerotic carotid arteries with microarray, 
      quantitative reverse transcription polymerase chain reaction, in situ 
      hybridization, and immunohistochemistry. RESULTS: Pimonidazole 
      immunohistochemistry demonstrated the presence of hypoxia, especially within the 
      macrophage-rich center of the lesions. Hypoxia correlated with the presence of a 
      thrombus, angiogenesis, and expression of CD68, HIF, and VEGF. The mRNA and 
      protein expression of HIF, its target genes, and microvessel density increased 
      from early to stable lesions, but no changes were observed between stable and 
      ruptured lesions. CONCLUSION: This is the first study directly demonstrating 
      hypoxia in advanced human atherosclerosis and its correlation with the presence 
      of macrophages and the expression of HIF and VEGF. Also, the HIF pathway was 
      associated with lesion progression and angiogenesis, suggesting its involvement 
      in the response to hypoxia and the regulation of human intraplaque angiogenesis.
FAU - Sluimer, Judith C
AU  - Sluimer JC
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), 
      University of Maastricht, Maastricht, The Netherlands.
FAU - Gasc, Jean-Marie
AU  - Gasc JM
FAU - van Wanroij, Job L
AU  - van Wanroij JL
FAU - Kisters, Natasja
AU  - Kisters N
FAU - Groeneweg, Mathijs
AU  - Groeneweg M
FAU - Sollewijn Gelpke, Maarten D
AU  - Sollewijn Gelpke MD
FAU - Cleutjens, Jack P
AU  - Cleutjens JP
FAU - van den Akker, Luc H
AU  - van den Akker LH
FAU - Corvol, Pierre
AU  - Corvol P
FAU - Wouters, Bradly G
AU  - Wouters BG
FAU - Daemen, Mat J
AU  - Daemen MJ
FAU - Bijnens, Ann-Pascale J
AU  - Bijnens AP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (Biomarkers)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Nitroimidazoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 46JO4D76R2 (pimonidazole)
SB  - IM
CIN - J Am Coll Cardiol. 2008 Apr 1;51(13):1266-7. PMID: 18371556
CIN - J Am Coll Cardiol. 2008 Sep 9;52(11):968; author reply 968-9. PMID: 18772074
MH  - Aged
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Biomarkers
MH  - Carotid Stenosis/*physiopathology
MH  - Cross-Sectional Studies
MH  - Disease Progression
MH  - Endarterectomy, Carotid
MH  - Female
MH  - Humans
MH  - Hypoxia/*physiopathology
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Immunohistochemistry
MH  - *Macrophages
MH  - Male
MH  - Middle Aged
MH  - *Neovascularization, Pathologic
MH  - Nitroimidazoles
MH  - *Oxidative Stress
MH  - RNA, Messenger
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2008/03/29 09:00
MHDA- 2008/04/30 09:00
CRDT- 2008/03/29 09:00
PHST- 2007/07/31 00:00 [received]
PHST- 2007/11/20 00:00 [revised]
PHST- 2007/12/10 00:00 [accepted]
PHST- 2008/03/29 09:00 [pubmed]
PHST- 2008/04/30 09:00 [medline]
PHST- 2008/03/29 09:00 [entrez]
AID - S0735-1097(08)00263-5 [pii]
AID - 10.1016/j.jacc.2007.12.025 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2008 Apr 1;51(13):1258-65. doi: 10.1016/j.jacc.2007.12.025.