PMID- 11845232
OWN - NLM
STAT- MEDLINE
DCOM- 20020509
LR  - 20220408
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 45
IP  - 1
DP  - 2002 Jan
TI  - Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration 
      of atherosclerosis in a diabetic pig model.
PG  - 125-33
AB  - AIMS/HYPOTHESIS: We previously showed that vascular smooth muscle cells and 
      endothelial cells cultured under high glucose conditions produced more 
      12(S)-hydroxyeicosatetraenoic acid (12-HETE), the 12-lipoxygenase (12-LO) product 
      of arachidonate metabolism, relative to normal glucose. Because the lipoxygenase 
      (LO) pathway has been associated with oxidant stress and the pathogenesis of 
      atherosclerosis, we now examined 12-LO activation in vivo in a pig model of 
      diabetes-induced accelerated atherosclerosis which displays human 
      characteristics. METHODS: The animal model was developed in pigs who were fed a 
      normal or high fat diet and given streptozotocin injections to produce 
      normolipemic-normoglycaemic (NLNG), normolipemic-hyperglycaemic (NLHG), 
      hyperlipemic-normoglycaemic (HLNG) and hyperlipemic-hyperglycaemic (HLHG) pigs. 
      Tissue samples were obtained from key arterial beds to examine 12-LO expression 
      at 20 weeks after the pigs began their diet. RESULTS: All HG pigs maintained 
      threefold higher serum glucose concentrations. The HL groups developed 
      atherosclerosis but diabetic HLHG pigs showed markedly accelerated 
      atherosclerosis (twofold) relative to non-diabetic HLNG pigs. Immunostaining 
      showed progressive increases in 12-LO in arteries in the order NLNG, NLHG, HLNG 
      and HLHG. Leukocyte-type 12-LO protein (immuno-blotting) as well as mRNA 
      expression (by competitive PCR) in abdominal and coronary arteries were 
      significantly greater in HLHG pigs than in all the other three groups. 
      Furthermore, increased oxidant stress was observed in monocytes from NLHG and 
      HLNG pigs, and greatly potentiated in HLHG pigs. CONCLUSIONS/INTERPRETATION: 
      These results are consistent with the hypothesis that 12-LO activation plays a 
      key role in accelerated atherosclerosis due to diabetes and hyperlipemia.
FAU - Natarajan, R
AU  - Natarajan R
AD  - Gonda Diabetes Center, Beckman Research Institute of the City of Hope, 1500 East 
      Duarte Road, Duarte, CA 91010, USA. Rnatarajan@coh.org
FAU - Gerrity, R G
AU  - Gerrity RG
FAU - Gu, J-L
AU  - Gu JL
FAU - Lanting, L
AU  - Lanting L
FAU - Thomas, L
AU  - Thomas L
FAU - Nadler, J L
AU  - Nadler JL
LA  - eng
GR  - R01 DK065073/DK/NIDDK NIH HHS/United States
GR  - CA 33572-15/CA/NCI NIH HHS/United States
GR  - P01 55798/PHS 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  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Blood Glucose)
RN  - 0 (Triglycerides)
RN  - 59985-28-3 (12-Hydroxy-5,8,10,14-eicosatetraenoic Acid)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
SB  - IM
MH  - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/urine
MH  - Animals
MH  - Aorta, Abdominal/pathology
MH  - Arachidonate 12-Lipoxygenase/genetics/*metabolism
MH  - Arteriosclerosis/pathology/*physiopathology
MH  - Blood Glucose/metabolism
MH  - Cholesterol/blood
MH  - Coronary Vessels/pathology
MH  - Diabetes Mellitus, Experimental/pathology/*physiopathology/urine
MH  - Diet, Atherogenic
MH  - Disease Progression
MH  - Hyperlipidemias/physiopathology
MH  - Male
MH  - Oxidative Stress/*physiology
MH  - Polymerase Chain Reaction
MH  - Swine
MH  - Triglycerides/blood
EDAT- 2002/02/15 10:00
MHDA- 2002/05/10 10:01
CRDT- 2002/02/15 10:00
PHST- 2002/02/15 10:00 [pubmed]
PHST- 2002/05/10 10:01 [medline]
PHST- 2002/02/15 10:00 [entrez]
AID - 10.1007/s125-002-8253-x [doi]
PST - ppublish
SO  - Diabetologia. 2002 Jan;45(1):125-33. doi: 10.1007/s125-002-8253-x.