PMID- 17255530
OWN - NLM
STAT- MEDLINE
DCOM- 20070425
LR  - 20220223
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 27
IP  - 4
DP  - 2007 Apr
TI  - Nrf2 gene transfer induces antioxidant enzymes and suppresses smooth muscle cell 
      growth in vitro and reduces oxidative stress in rabbit aorta in vivo.
PG  - 741-7
AB  - BACKGROUND: Reactive oxygen species (ROS) play a major role in vascular 
      inflammation and pathophysiology of many vascular diseases such as 
      atherosclerosis and injury-induced neointima formation after balloon angioplasty. 
      Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor orchestrating 
      antioxidant and cytoprotective responses on oxidative and electrophilic stress, 
      and it has been shown to have antiinflammatory effects in vascular cells in 
      vitro. We therefore postulated that Nrf2 gene transfer would have salutary 
      effects on vascular inflammation after angioplasty. METHODS AND RESULTS: 
      Transduction of vascular smooth muscle cells (VSMCs) with Nrf2-expressing 
      adenovirus increased the expression of several antioxidant enzymes including heme 
      oxygenase-1 (HO-1) compared with beta-galactosidase (AdLacZ)-transduced controls. 
      Moreover, Nrf2 gene transfer also inhibited vascular smooth muscle cell (VSMC) 
      proliferation, and the effect was partially reversed by the HO inhibitor Sn(IV) 
      protoporphyrin. In vivo, adenoviral gene transfer effectively reduced oxidative 
      stress determined by antibody staining against oxidized epitopes of LDL, as well 
      as inhibited vascular inflammation assessed by the macrophage cell count and 
      monocyte chemoattractant protein-1 (MCP-1) staining. However, the 
      antiproliferative effects of Nrf2 in vivo were counterbalanced with diminished 
      apoptosis in neointimal VSMCs, resulting in no change in neointimal hyperplasia. 
      CONCLUSIONS: Nrf2 gene transfer or Nrf2-inducing drugs may have therapeutic 
      applications in vascular diseases in which inflammation and oxidative stress play 
      a role. However, the contrasting growth inhibitory and antiapoptotic effects of 
      Nrf2 need to be considered in pathological conditions in which SMC proliferation 
      plays a critical role.
FAU - Levonen, Anna-Liisa
AU  - Levonen AL
AD  - Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, 
      University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. 
      Anna-Liisa.Levonen@uku.fi
FAU - Inkala, Matias
AU  - Inkala M
FAU - Heikura, Tommi
AU  - Heikura T
FAU - Jauhiainen, Suvi
AU  - Jauhiainen S
FAU - Jyrkkanen, Henna-Kaisa
AU  - Jyrkkanen HK
FAU - Kansanen, Emilia
AU  - Kansanen E
FAU - Maatta, Kirsi
AU  - Maatta K
FAU - Romppanen, Elina
AU  - Romppanen E
FAU - Turunen, Paivi
AU  - Turunen P
FAU - Rutanen, Juha
AU  - Rutanen J
FAU - Yla-Herttuala, Seppo
AU  - Yla-Herttuala S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070125
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
SB  - IM
MH  - Animals
MH  - Aorta/injuries/*metabolism/pathology
MH  - Apoptosis
MH  - Arteritis/etiology/pathology/physiopathology
MH  - Catheterization/adverse effects
MH  - Cell Division
MH  - Cell Proliferation
MH  - Endothelium, Vascular/physiopathology
MH  - Gene Expression Regulation
MH  - *Gene Transfer Techniques
MH  - Heme Oxygenase-1/metabolism
MH  - Humans
MH  - Hyperplasia
MH  - Myocytes, Smooth Muscle/*cytology
MH  - NAD(P)H Dehydrogenase (Quinone)/metabolism
MH  - NF-E2-Related Factor 2/*genetics/metabolism
MH  - *Oxidative Stress
MH  - Oxidoreductases/genetics/*metabolism
MH  - Rabbits
MH  - Tunica Intima/pathology/physiopathology
EDAT- 2007/01/27 09:00
MHDA- 2007/04/26 09:00
CRDT- 2007/01/27 09:00
PHST- 2007/01/27 09:00 [pubmed]
PHST- 2007/04/26 09:00 [medline]
PHST- 2007/01/27 09:00 [entrez]
AID - 01.ATV.0000258868.80079.4d [pii]
AID - 10.1161/01.ATV.0000258868.80079.4d [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):741-7. doi: 
      10.1161/01.ATV.0000258868.80079.4d. Epub 2007 Jan 25.