PMID- 25476109
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20150224
IS  - 1879-016X (Electronic)
IS  - 0163-7258 (Linking)
VI  - 148
DP  - 2015 Apr
TI  - Role of copper in regression of cardiac hypertrophy.
PG  - 66-84
LID - S0163-7258(14)00214-9 [pii]
LID - 10.1016/j.pharmthera.2014.11.014 [doi]
AB  - Pressure overload causes an accumulation of homocysteine in the heart, which is 
      accompanied by copper depletion through the formation of copper-homocysteine 
      complexes and the excretion of the complexes. Copper supplementation recovers 
      cytochrome c oxidase (CCO) activity and promotes myocardial angiogenesis, along 
      with the regression of cardiac hypertrophy and the recovery of cardiac 
      contractile function. Increased copper availability is responsible for the 
      recovery of CCO activity. Copper promoted expression of angiogenesis factors 
      including vascular endothelial growth factor (VEGF) in endothelial cells is 
      responsible for angiogenesis. VEGF receptor-2 (VEGFR-2) is critical for 
      hypertrophic growth of cardiomyocytes and VEGFR-1 is essential for the regression 
      of cardiomyocyte hypertrophy. Copper, through promoting VEGF production and 
      suppressing VEGFR-2, switches the VEGF signaling pathway from VEGFR-2-dependent 
      to VEGFR-1-dependent, leading to the regression of cardiomyocyte hypertrophy. 
      Copper is also required for hypoxia-inducible factor-1 (HIF-1) transcriptional 
      activity, acting on the interaction between HIF-1 and the hypoxia responsible 
      element and the formation of HIF-1 transcriptional complex by inhibiting the 
      factor inhibiting HIF-1. Therefore, therapeutic targets for copper 
      supplementation-induced regression of cardiac hypertrophy include: (1) the 
      recovery of copper availability for CCO and other critical cellular events; (2) 
      the activation of HIF-1 transcriptional complex leading to the promotion of 
      angiogenesis in the endothelial cells by VEGF and other factors; (3) the 
      activation of VEGFR-1-dependent regression signaling pathway in the 
      cardiomyocytes; and (4) the inhibition of VEGFR-2 through post-translational 
      regulation in the hypertrophic cardiomyocytes. Future studies should focus on 
      target-specific delivery of copper for the development of clinical application.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Zheng, Lily
AU  - Zheng L
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Han, Pengfei
AU  - Han P
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Liu, Jiaming
AU  - Liu J
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Li, Rui
AU  - Li R
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Yin, Wen
AU  - Yin W
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Wang, Tao
AU  - Wang T
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Zhang, Wenjing
AU  - Zhang W
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Kang, Y James
AU  - Kang YJ
AD  - Regenerative Medicine Research Center, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China; Department of Pharmacology and Toxicology, 
      University of Louisville, Louisville, KY 40292, USA. Electronic address: 
      jameskang@vip.163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20141201
PL  - England
TA  - Pharmacol Ther
JT  - Pharmacology & therapeutics
JID - 7905840
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 789U1901C5 (Copper)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Animals
MH  - Cardiomegaly/*metabolism
MH  - Copper/*metabolism
MH  - Electron Transport Complex IV/metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/metabolism
MH  - Myocytes, Cardiac/metabolism
MH  - Neovascularization, Physiologic
OTO - NOTNLM
OT  - Angiogenesis
OT  - CCO
OT  - Cardiac hypertrophy
OT  - Copper
OT  - HIF-1
OT  - VEGFRs
EDAT- 2014/12/06 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/06 06:00
PHST- 2014/11/17 00:00 [received]
PHST- 2014/11/17 00:00 [accepted]
PHST- 2014/12/06 06:00 [entrez]
PHST- 2014/12/06 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0163-7258(14)00214-9 [pii]
AID - 10.1016/j.pharmthera.2014.11.014 [doi]
PST - ppublish
SO  - Pharmacol Ther. 2015 Apr;148:66-84. doi: 10.1016/j.pharmthera.2014.11.014. Epub 
      2014 Dec 1.