PMID- 21752377
OWN - NLM
STAT- MEDLINE
DCOM- 20120405
LR  - 20231213
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 219
IP  - 2
DP  - 2011 Dec
TI  - Ursolic acid protects diabetic mice against monocyte dysfunction and accelerated 
      atherosclerosis.
PG  - 409-16
LID - 10.1016/j.atherosclerosis.2011.06.013 [doi]
AB  - AIMS: Accelerated atherosclerosis is a major diabetic complication initiated by 
      the enhanced recruitment of monocytes into the vasculature. In this study, we 
      examined the therapeutic potential of the phytonutrients ursolic acid (UA) and 
      resveratrol (RES) in preventing monocyte recruitment and accelerated 
      atherosclerosis. METHODS AND RESULTS: Dietary supplementation with either RES or 
      UA (0.2%) protected against accelerated atherosclerosis induced by streptozotocin 
      in high-fat diet-fed LDL receptor-deficient mice. However, mice that received 
      dietary UA for 11 weeks were significantly better protected and showed a 53% 
      reduction in lesion formation while mice fed a RES-supplemented diet showed only 
      a 31% reduction in lesion size. Importantly, UA was also significantly more 
      effective in preventing the appearance of proinflammatory GR-1(high) monocytes 
      induced by these diabetic conditions and reducing monocyte recruitment into 
      MCP-1-loaded Matrigel plugs implanted into these diabetic mice. Oxidatively 
      stressed THP-1 monocytes mimicked the behavior of blood monocytes in diabetic 
      mice and showed enhanced responsiveness to monocyte chemoattractant protein-1 
      (MCP-1) without changing MCP-1 receptor (CCR2) surface expression. Pretreatment 
      of THP-1 monocytes with RES or UA (0.3-10muM) for 15h resulted in the 
      dose-dependent inhibition of H(2)O(2)-accelerated chemotaxis in response to 
      MCP-1, but with an IC(50) of 0.4muM, UA was 2.7-fold more potent than RES. 
      CONCLUSION: Dietary UA is a potent inhibitor of monocyte dysfunction and 
      accelerated atherosclerosis induced by diabetes. These studies identify ursolic 
      acid as a potential therapeutic agent for the treatment of diabetic 
      complications, including accelerated atherosclerosis, and provide a novel 
      mechanism for the anti-atherogenic properties of ursolic acid.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Ullevig, Sarah L
AU  - Ullevig SL
AD  - Department of Biochemistry, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX 78229-3900, United States.
FAU - Zhao, Qingwei
AU  - Zhao Q
FAU - Zamora, Debora
AU  - Zamora D
FAU - Asmis, Reto
AU  - Asmis R
LA  - eng
GR  - R01 HL070963/HL/NHLBI NIH HHS/United States
GR  - R01 HL070963-08/HL/NHLBI NIH HHS/United States
GR  - T32 HL007446/HL/NHLBI NIH HHS/United States
GR  - HL-70963/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110617
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, LDL)
RN  - 0 (Stilbenes)
RN  - 0 (Triterpenes)
RN  - Q369O8926L (Resveratrol)
SB  - IM
CIN - Atherosclerosis. 2011 Dec;219(2):397-8. PMID: 21993411
MH  - Animals
MH  - Aortic Diseases/etiology/immunology/*prevention & control
MH  - Atherosclerosis/etiology/immunology/*prevention & control
MH  - Cardiovascular Agents/*pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Chemotaxis, Leukocyte/drug effects
MH  - Diabetes Mellitus, Experimental/complications/*drug 
      therapy/immunology/physiopathology
MH  - Diabetic Angiopathies/etiology/immunology/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Hyperlipidemias/complications/genetics/metabolism
MH  - Kidney/drug effects/physiopathology
MH  - Macrophages/drug effects/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocytes/*drug effects/immunology
MH  - Oxidative Stress/drug effects
MH  - Receptors, CCR2/metabolism
MH  - Receptors, LDL/deficiency/genetics
MH  - Resveratrol
MH  - Stilbenes/pharmacology
MH  - Time Factors
MH  - Triterpenes/*pharmacology
MH  - Ursolic Acid
PMC - PMC3199329
MID - NIHMS311567
EDAT- 2011/07/15 06:00
MHDA- 2012/04/06 06:00
PMCR- 2012/12/01
CRDT- 2011/07/15 06:00
PHST- 2011/04/27 00:00 [received]
PHST- 2011/05/20 00:00 [revised]
PHST- 2011/06/06 00:00 [accepted]
PHST- 2011/07/15 06:00 [entrez]
PHST- 2011/07/15 06:00 [pubmed]
PHST- 2012/04/06 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - S0021-9150(11)00494-1 [pii]
AID - 10.1016/j.atherosclerosis.2011.06.013 [doi]
PST - ppublish
SO  - Atherosclerosis. 2011 Dec;219(2):409-16. doi: 
      10.1016/j.atherosclerosis.2011.06.013. Epub 2011 Jun 17.