PMID- 19666844
OWN - NLM
STAT- MEDLINE
DCOM- 20091008
LR  - 20211020
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 297
IP  - 4
DP  - 2009 Oct
TI  - Role of MCP-1 in tumor necrosis factor-alpha-induced endothelial dysfunction in 
      type 2 diabetic mice.
PG  - H1208-16
LID - 10.1152/ajpheart.00396.2009 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) upregulates the expression of monocyte 
      chemoattractant protein-1 (MCP-1) and adhesion molecules in type 2 diabetes. We 
      hypothesized that TNF-alpha and MCP-1 may interact to contribute to the evolution 
      of vascular inflammation and endothelial dysfunction in coronary arterioles in 
      type 2 diabetes. To test this hypothesis, we administered anti-MCP-1 to block 
      MCP-1 signaling in genetically modified mice with type 2 diabetes (Lepr(db)) and 
      in heterozygote (m Lepr(db)) lean control. Anti-MCP-1 partially restored 
      vasodilation to the endothelium-dependent vasodilator acetylcholine in isolated, 
      cannulated, and pressurized coronary arterioles in Lepr(db) mice but did not 
      affect vasodilation in m Lepr(db) mice. Anti-MCP-1 attenuated superoxide 
      production and the protein expression of nitrotyrosine, which is an indicator of 
      peroxynitrite production, in isolated coronary arterioles of Lepr(db) mice. 
      Immunostaining results showed that the expression of MCP-1 and vascular cellular 
      adhesion molecule-1 is colocalized with endothelial cells and macrophages. 
      Anti-TNF-alpha or anti-MCP-1 markedly reduced macrophage infiltration and the 
      number of MCP-1-positive endothelium in Lepr(db) mice. The neutralization of 
      TNF-alpha or anti-MCP-1 reduced the expression of adhesion molecules, suggesting 
      that proinflammatory cytokines interact to amplify the signaling process that 
      leads to vascular dysfunction. These findings demonstrate that the endothelial 
      dysfunction occurring in type 2 diabetes is the result of the effects of the 
      inflammatory cytokine TNF-alpha and TNF-alpha-related signaling, including the 
      expression of MCP-1 and adhesion molecules, which further exacerbates vessel 
      inflammation and oxidative stress.
FAU - Yang, Jiyeon
AU  - Yang J
AD  - Michael E DeBakey Institute, Texas A&M University, College Station, Texas, USA.
FAU - Park, Yoonjung
AU  - Park Y
FAU - Zhang, Hanrui
AU  - Zhang H
FAU - Gao, Xue
AU  - Gao X
FAU - Wilson, Emily
AU  - Wilson E
FAU - Zimmer, Warren
AU  - Zimmer W
FAU - Abbott, Louise
AU  - Abbott L
FAU - Zhang, Cuihua
AU  - Zhang C
LA  - eng
GR  - R01-HL-077566/HL/NHLBI NIH HHS/United States
GR  - R01-HL-085119/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 - 20090807
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Leptin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (Vasodilator Agents)
RN  - 0 (leptin receptor, mouse)
RN  - 11062-77-4 (Superoxides)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 452VLY9402 (Serine)
SB  - IM
MH  - Animals
MH  - Arterioles/metabolism/physiopathology
MH  - Biomarkers/blood
MH  - Chemokine CCL2/*metabolism
MH  - Coronary Vessels/drug effects/*metabolism/physiopathology
MH  - Diabetes Mellitus, Type 2/genetics/*metabolism/physiopathology
MH  - Diabetic Angiopathies/genetics/*metabolism/physiopathology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/drug effects/*metabolism/physiopathology
MH  - Female
MH  - I-kappa B Proteins/metabolism
MH  - Inflammation Mediators/*metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress
MH  - Peroxynitrous Acid/metabolism
MH  - Phosphorylation
MH  - Receptors, Leptin/genetics
MH  - Serine
MH  - Signal Transduction
MH  - Superoxides/metabolism
MH  - Tumor Necrosis Factor-alpha/deficiency/genetics/*metabolism
MH  - Tyrosine/analogs & derivatives/metabolism
MH  - Vascular Cell Adhesion Molecule-1/metabolism
MH  - *Vasodilation/drug effects
MH  - Vasodilator Agents/pharmacology
PMC - PMC2770760
EDAT- 2009/08/12 09:00
MHDA- 2009/10/09 06:00
PMCR- 2010/10/01
CRDT- 2009/08/12 09:00
PHST- 2009/08/12 09:00 [entrez]
PHST- 2009/08/12 09:00 [pubmed]
PHST- 2009/10/09 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 00396.2009 [pii]
AID - H-00396-2009 [pii]
AID - 10.1152/ajpheart.00396.2009 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1208-16. doi: 
      10.1152/ajpheart.00396.2009. Epub 2009 Aug 7.