PMID- 21477627
OWN - NLM
STAT- MEDLINE
DCOM- 20111027
LR  - 20220408
IS  - 1872-8294 (Electronic)
IS  - 0169-409X (Linking)
VI  - 63
IP  - 8
DP  - 2011 Jul 18
TI  - The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in 
      cardiovascular and malignant diseases.
PG  - 597-609
LID - 10.1016/j.addr.2011.03.006 [doi]
AB  - Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically 
      active eicosanoids. The primary epoxidation products are four regioisomers of 
      cis-epoxyeicosatrienoic acid (EET): 5,6-, 8,9-, 11,12-, and 14,15-EET. CYP2J2, 
      CYP2C8, and CYP2C9 are the predominant epoxygenase isoforms involved in EET 
      formation. CYP2J and CYP2C gene families in humans are abundantly expressed in 
      the endothelium, myocardium, and kidney. The cardiovascular effects of CYP 
      epoxygenases and EETs range from vasodilation, anti-hypertension, 
      pro-angiogenesis, anti-atherosclerosis, and anti-inflammation to anti-injury 
      caused by ischemia-reperfusion. Using transgenic animals for in vivo analyses of 
      CYP epoxygenases revealed comprehensive and marked cardiovascular protective 
      effects. In contrast, CYP epoxygenases and their metabolites, EETs, are 
      upregulated in human tumors and promote tumor progression and metastasis. These 
      biological effects result from the anti-apoptosis, pro-mitogenesis, and 
      anti-migration roles of CYP epoxygenases and EETs at the cellular level. 
      Importantly, soluble epoxide hydrolase (sEH) inhibitors are anti-hypertensive and 
      anti-inflammatory and, therefore, protect the heart from damage, whereas the 
      terfenadine-related, specific inhibitors of CYP2J2 exhibit strong anti-tumor 
      activity in vitro and in vivo. Thus, CYP2J2 and arachidonic acid-derived 
      metabolites likely play important roles in regulating cardiovascular functions 
      and malignancy under physiological and/or pathological conditions. Moreover, 
      although challenges remain to improving the drug-like properties of sEH 
      inhibitors and identifying efficient ways to deliver sEH inhibitors, sEH will 
      likely become an important therapeutic target for cardiovascular diseases. In 
      addition, CYP2J2 may be a therapeutic target for treating human cancers and 
      leukemia.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Xu, Xizhen
AU  - Xu X
AD  - Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, 
      Tongji Medical College of Huazhong University of Science and Technology, Wuhan 
      430030, PR China.
FAU - Zhang, Xin A
AU  - Zhang XA
FAU - Wang, Dao Wen
AU  - Wang DW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110406
PL  - Netherlands
TA  - Adv Drug Deliv Rev
JT  - Advanced drug delivery reviews
JID - 8710523
RN  - 0 (Arachidonic Acids)
RN  - 0 (CYP2J2 protein, human)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2J2)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Arachidonic Acid/metabolism
MH  - Arachidonic Acids/*metabolism
MH  - Cardiovascular Diseases/drug therapy/*physiopathology
MH  - Cytochrome P-450 CYP2J2
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Drug Delivery Systems
MH  - Humans
MH  - Neoplasms/drug therapy/*physiopathology
EDAT- 2011/04/12 06:00
MHDA- 2011/10/28 06:00
CRDT- 2011/04/12 06:00
PHST- 2010/11/09 00:00 [received]
PHST- 2011/02/03 00:00 [revised]
PHST- 2011/03/19 00:00 [accepted]
PHST- 2011/04/12 06:00 [entrez]
PHST- 2011/04/12 06:00 [pubmed]
PHST- 2011/10/28 06:00 [medline]
AID - S0169-409X(11)00054-8 [pii]
AID - 10.1016/j.addr.2011.03.006 [doi]
PST - ppublish
SO  - Adv Drug Deliv Rev. 2011 Jul 18;63(8):597-609. doi: 10.1016/j.addr.2011.03.006. 
      Epub 2011 Apr 6.