PMID- 19355887
OWN - NLM
STAT- MEDLINE
DCOM- 20090709
LR  - 20190823
IS  - 0929-8673 (Print)
IS  - 0929-8673 (Linking)
VI  - 16
IP  - 10
DP  - 2009
TI  - Role of copper in angiogenesis and its medicinal implications.
PG  - 1304-14
AB  - Copper promotion of angiogenesis has been known for more than two decades, but 
      the mechanism of action of copper has not been explored until recently. Copper 
      stimulation of factors involved in vessel formation and maturation, such as 
      vascular endothelial growth factor (VEGF), is mainly responsible for its 
      angiogenesis effect. Copper is required for the activation of hypoxia-inducible 
      factor-1 (HIF-1), a major transcription factor regulating the expression of VEGF. 
      Copper would be transported into nucleus by a copper chaperon for superoxide 
      dismutase-1. Copper is required for HIF-1 interaction with the hypoxia-responsive 
      element of the target genes and ensures the formation of HIF-1 transcriptional 
      complex, thus activating the expression of target genes including VEGF. On the 
      other hand, excess copper can stabilize HIF-1alpha, the rate-limiting component 
      of HIF-1, leading to its accumulation in cytoplasm and thus HIF-1 activation. The 
      essential role of copper in production of VEGF makes it implicated in 
      anti-angiogenesis therapy, such as the application of copper chelators in cancer 
      therapy. However, suppression of angiogenesis is involved in the progression of 
      heart hypertrophy and its transition to heart failure, therefore copper 
      supplementation improves hypertrophic heart disease conditions. This dilemma of 
      copper implications in cancer therapy and heart hypertrophy dictates a 
      comprehensive understanding of a patient's condition before an implementation of 
      copper manipulation therapy for different diseases. In this context, a 
      development of diagnosis for copper metabolic changes as well as a 
      tissue-specific copper manipulation would greatly benefit patients with an 
      implication of copper manipulation therapy.
FAU - Xie, Huiqi
AU  - Xie H
AD  - Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, 
      West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
FAU - Kang, Y James
AU  - Kang YJ
LA  - eng
GR  - HL59225/HL/NHLBI NIH HHS/United States
GR  - HL63760/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 789U1901C5 (Copper)
SB  - IM
MH  - Antineoplastic Agents/therapeutic use
MH  - Copper/*pharmacology/*therapeutic use
MH  - Heart Diseases/drug therapy
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/drug effects
MH  - Neoplasms/*drug therapy
MH  - *Neovascularization, Physiologic/drug effects
MH  - Vascular Endothelial Growth Factor A/drug effects
EDAT- 2009/04/10 09:00
MHDA- 2009/07/10 09:00
CRDT- 2009/04/10 09:00
PHST- 2009/04/10 09:00 [entrez]
PHST- 2009/04/10 09:00 [pubmed]
PHST- 2009/07/10 09:00 [medline]
AID - 10.2174/092986709787846622 [doi]
PST - ppublish
SO  - Curr Med Chem. 2009;16(10):1304-14. doi: 10.2174/092986709787846622.