PMID- 11245651
OWN - NLM
STAT- MEDLINE
DCOM- 20010524
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 103
IP  - 10
DP  - 2001 Mar 13
TI  - Ribozyme-mediated inhibition of rat leukocyte-type 12-lipoxygenase prevents 
      intimal hyperplasia in balloon-injured rat carotid arteries.
PG  - 1446-52
AB  - BACKGROUND: 12-Lipoxygenase (12-LO) products of arachidonate metabolism have 
      growth and chemotactic effects in vascular smooth muscle cells. We have also 
      recently demonstrated increased 12-LO mRNA and protein expression in the 
      neointima of balloon-injured rat carotid arteries. In this study, we evaluated 
      whether 12-LO activation plays a role in neointimal thickening in this rat model 
      by using a specific ribozyme (Rz) directed to rat 12-LO. METHODS AND RESULTS: We 
      designed a chimeric DNA-RNA hammerhead Rz to cleave rat leukocyte-type 12-LO 
      mRNA. This Rz dose-dependently cleaved a 166-nucleotide target 12-LO mRNA 
      substrate in vitro and reduced 12-LO mRNA and protein expression in rat vascular 
      smooth muscle cells. A control mutant Rz (MRz) with a point mutation in the 
      catalytic site was inactive. To test the in vivo efficacy of the 12-LO Rz, the 
      left common carotid arteries of rats were injured with a balloon catheter. The 
      distal half of the injured arteries was treated with Rz or MRz mixed with 
      lipofectin. The proximal half received only lipofectin. Twelve days after injury, 
      intima-to-media ratios were significantly lower in the Rz-treated sections than 
      in untreated sections from the same rat (0.742+/-0.16 versus 1.749+/-0.12, 
      P:<0.001). In contrast, the MRz had no significant effect. CONCLUSIONS: These 
      results indicate the important role of the leukocyte-type 12-LO pathway in 
      restenosis in response to injury.
FAU - Gu, J L
AU  - Gu JL
AD  - Division of Endocrinology and Metabolism, University of Virginia Health Science 
      Center, Charlottesville, VA, 22908, USA.
FAU - Pei, H
AU  - Pei H
FAU - Thomas, L
AU  - Thomas L
FAU - Nadler, J L
AU  - Nadler JL
FAU - Rossi, J J
AU  - Rossi JJ
FAU - Lanting, L
AU  - Lanting L
FAU - Natarajan, R
AU  - Natarajan R
LA  - eng
GR  - CA-33572-15/CA/NCI NIH HHS/United States
GR  - P01 HL-55798/HL/NHLBI 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  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Contrast Media)
RN  - 0 (Fibronectins)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (RNA, Catalytic)
RN  - 0 (RNA, Messenger)
RN  - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
RN  - TPY09G7XIR (Fluorescein)
SB  - IM
MH  - Analysis of Variance
MH  - Angioplasty, Balloon, Coronary/adverse effects
MH  - Animals
MH  - Arachidonate 12-Lipoxygenase/genetics/*metabolism
MH  - Carotid Artery Diseases/etiology/*prevention & control
MH  - Cell Movement/drug effects
MH  - Contrast Media/metabolism
MH  - Disease Models, Animal
MH  - Fibronectins/metabolism
MH  - Fluorescein/metabolism
MH  - Hyperplasia/etiology/prevention & control
MH  - Leukocytes/*enzymology
MH  - Lipoxygenase Inhibitors
MH  - Male
MH  - RNA, Catalytic/genetics/metabolism/*therapeutic use
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transfection
MH  - Tunica Intima/*pathology
EDAT- 2001/03/14 10:00
MHDA- 2001/05/26 10:01
CRDT- 2001/03/14 10:00
PHST- 2001/03/14 10:00 [pubmed]
PHST- 2001/05/26 10:01 [medline]
PHST- 2001/03/14 10:00 [entrez]
AID - 10.1161/01.cir.103.10.1446 [doi]
PST - ppublish
SO  - Circulation. 2001 Mar 13;103(10):1446-52. doi: 10.1161/01.cir.103.10.1446.