PMID- 20075419
OWN - NLM
STAT- MEDLINE
DCOM- 20100416
LR  - 20121115
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 30
IP  - 4
DP  - 2010 Apr
TI  - Effects of caspase inhibitor on angiotensin II-induced abdominal aortic aneurysm 
      in apolipoprotein E-deficient mice.
PG  - 702-7
LID - 10.1161/ATVBAHA.109.200527 [doi]
AB  - OBJECTIVE: The presence of apoptotic markers is a prominent histological feature 
      of abdominal aortic aneurysm. To understand the role of apoptosis in the 
      pathogenesis of this common vascular disease, we tested the effect of the 
      pan-caspase inhibitor quinoline-Val-Asp-difluorophenoxymethylketone (Q-VD-OPh) on 
      aneurysm formation using a mouse angiotensin II (Ang II) model. METHODS AND 
      RESULTS: Ang II in apolipoprotein E-deficient mice significantly induced medial 
      cell apoptosis 3 days after infusion at the aortic region, eventually becoming 
      aneurismal. A daily administration of 20 mg/kg per day Q-VD-OPh starting 6 hours 
      before Ang II infusion reduced aneurysm incidence from 83.3% to 16.7% and maximal 
      aortic diameter from 2.43+/-0.29 mm to 1.58+/-0.18 mm. The caspase inhibitor 
      treated mice showed profoundly diminished levels of medial apoptosis and 
      inflammation. In contrast, administration of Q-VD-OPh starting 7 days after Ang 
      II infusion had no significant impact on aneurysm development. In vitro, media 
      conditioned by Ang II-treated smooth muscle cells (SMCs) stimulated macrophage 
      chemotaxis in a caspase-dependent manner. Inhibition of monocyte chemoattractant 
      protein-1 (MCP-1) in the conditioned media via a neutralizing antibody completely 
      blocked the ability of conditioned media to attract macrophages. CONCLUSIONS: 
      These results indicate that medial SMC apoptosis may contribute to vascular 
      inflammation and thus aneurysm formation, in part through production of MCP-1.
FAU - Yamanouchi, Dai
AU  - Yamanouchi D
AD  - Division of Vascular Surgery, Department of Surgery, University of 
      Wisconsin-Madison, 1111 Highland Avenue, WIMR 5120, Madison, WI 53705, USA.
FAU - Morgan, Stephanie
AU  - Morgan S
FAU - Kato, Kaori
AU  - Kato K
FAU - Lengfeld, Justin
AU  - Lengfeld J
FAU - Zhang, Fan
AU  - Zhang F
FAU - Liu, Bo
AU  - Liu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100114
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Quinolines)
RN  - 0 (quinoline-val-asp(OMe)-CH2-OPH)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/*pharmacology
MH  - Angiotensin II
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/chemically induced/*drug 
      therapy/enzymology/genetics/pathology
MH  - Apolipoproteins E/*deficiency/genetics
MH  - Apoptosis/*drug effects
MH  - *Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Chemotaxis/drug effects
MH  - Culture Media, Conditioned/metabolism
MH  - Disease Models, Animal
MH  - Macrophages/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/*drug effects/enzymology/pathology
MH  - Myocytes, Smooth Muscle/*drug effects/enzymology/pathology
MH  - Protease Inhibitors/*pharmacology
MH  - Quinolines/*pharmacology
MH  - Severity of Illness Index
MH  - Time Factors
EDAT- 2010/01/16 06:00
MHDA- 2010/04/17 06:00
CRDT- 2010/01/16 06:00
PHST- 2010/01/16 06:00 [entrez]
PHST- 2010/01/16 06:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
AID - ATVBAHA.109.200527 [pii]
AID - 10.1161/ATVBAHA.109.200527 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):702-7. doi: 
      10.1161/ATVBAHA.109.200527. Epub 2010 Jan 14.