PMID- 10699162
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20220408
IS  - 0028-4793 (Print)
IS  - 0028-4793 (Linking)
VI  - 342
IP  - 9
DP  - 2000 Mar 2
TI  - Early expression of angiogenesis factors in acute myocardial ischemia and 
      infarction.
PG  - 626-33
AB  - BACKGROUND: When the myocardium is deprived of blood, a process of ischemia, 
      infarction, and myocardial remodeling is initiated. Hypoxia-inducible factor 1 
      (HIF-1) is a transcriptional activator of vascular endothelial growth factor 
      (VEGF) and is critical for initiating early cellular responses to hypoxia. We 
      investigated the temporal and spatial patterns of expression of the alpha subunit 
      of HIF-1 (HIF-1alpha) and VEGF in specimens of human heart tissue to elucidate 
      the early molecular responses to myocardial hypoxia. METHODS: Ventricular-biopsy 
      specimens from 37 patients undergoing coronary bypass surgery were collected. The 
      specimens were examined by microscopy for evidence of ischemia, evolving 
      infarction, or a normal histologic appearance. The specimens were also analyzed 
      with the reverse-transcriptase polymerase chain reaction for HIF-1alpha and VEGF 
      messenger RNA (mRNA) expression and by immunohistochemical analysis for the 
      location of the HIF-1alpha and VEGF proteins. RESULTS: HIF-1alpha mRNA was 
      detected in myocardial specimens with pathological evidence of acute ischemia 
      (onset, <48 hours before surgery) or early infarction (onset, <24 hours before 
      surgery). In contrast, VEGF transcripts were seen in specimens with evidence of 
      acute ischemia or evolving infarction (onset, 24 to 120 hours before surgery). 
      Patients with normal ventricles or evidence of infarction in the distant past had 
      no detectable levels of either VEGF mRNA or HIF-1alpha mRNA. HIF-1alpha 
      immunoreactivity was detected in the nuclei of myocytes and endothelial cells, 
      whereas VEGF immunoreactivity was found in the cytoplasm of endothelial cells 
      lining capillaries and arterioles. CONCLUSIONS: An increase in the level of 
      HIF-1alpha is an early response to myocardial ischemia or infarction. This 
      response defines, at a molecular level, one of the first adaptations of human 
      myocardium to a deprivation of blood. HIF-1alpha is a useful temporal marker of 
      acutely jeopardized myocardium.
FAU - Lee, S H
AU  - Lee SH
AD  - Division of Cardiothoracic Surgery, University of California, San Diego, 
      92103-8892, USA.
FAU - Wolf, P L
AU  - Wolf PL
FAU - Escudero, R
AU  - Escudero R
FAU - Deutsch, R
AU  - Deutsch R
FAU - Jamieson, S W
AU  - Jamieson SW
FAU - Thistlethwaite, P A
AU  - Thistlethwaite PA
LA  - eng
GR  - MO1 RR 0827/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
CIN - N Engl J Med. 2000 Jul 13;343(2):148-9. PMID: 10896559
MH  - Acute Disease
MH  - Aged
MH  - Angiogenesis Inducing Agents/genetics/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Endothelial Growth Factors/genetics/*metabolism
MH  - Female
MH  - Heart Ventricles/pathology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Lymphokines/genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction/*metabolism/pathology
MH  - Myocardial Ischemia/*metabolism/pathology
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Prospective Studies
MH  - RNA, Messenger/genetics
MH  - Transcription Factors/genetics/*metabolism
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2000/03/04 00:00
MHDA- 2000/03/04 00:01
CRDT- 2000/03/04 00:00
PHST- 2000/03/04 00:00 [pubmed]
PHST- 2000/03/04 00:01 [medline]
PHST- 2000/03/04 00:00 [entrez]
AID - 10.1056/NEJM200003023420904 [doi]
PST - ppublish
SO  - N Engl J Med. 2000 Mar 2;342(9):626-33. doi: 10.1056/NEJM200003023420904.