PMID- 26993251
OWN - NLM
STAT- MEDLINE
DCOM- 20170411
LR  - 20170411
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 130
IP  - 12
DP  - 2016 Jun 1
TI  - Paraoxonase-1 overexpression prevents experimental abdominal aortic aneurysm 
      progression.
PG  - 1027-38
LID - 10.1042/CS20160185 [doi]
AB  - Abdominal aortic aneurysm (AAA) is a permanent dilation of the aorta due to 
      excessive proteolytic, oxidative and inflammatory injury of the aortic wall. We 
      aimed to identify novel mediators involved in AAA pathophysiology, which could 
      lead to novel therapeutic approaches. For that purpose, plasma from four AAA 
      patients and four controls were analysed by a label-free proteomic approach. 
      Among identified proteins, paraoxonase-1 (PON1) was decreased in plasma of AAA 
      patients compared with controls, which was further validated in a bigger cohort 
      of samples by ELISA. The phenylesterase enzymatic activity of PON1 was also 
      decreased in serum of AAA patients compared with controls. To address the 
      potential role of PON1 as a mediator of AAA, experimental AAA was induced by 
      aortic elastase perfusion in wild-type (WT) mice and human transgenic PON1 
      (HuTgPON1) mice. Similar to humans, PON1 activity was also decreased in serum of 
      elastase-induced AAA mice compared with healthy mice. Interestingly, 
      overexpression of PON1 was accompanied by smaller aortic dilation and higher 
      elastin and vascular smooth muscle cell (VSMC) content in the AAA of HuTgPON1 
      compared with WT mice. Moreover, HuTgPON1 mice display decreased oxidative stress 
      and apoptosis, as well as macrophage infiltration and monocyte chemoattractant 
      protein-1 (MCP1) expression, in elastase-induced AAA. In conclusion, decreased 
      circulating PON1 activity is associated with human and experimental AAA. PON1 
      overexpression in mice protects against AAA progression by reducing oxidative 
      stress, apoptosis and inflammation, suggesting that strategies aimed at 
      increasing PON1 activity could prevent AAA.
CI  - (c) 2016 The Author(s). published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Burillo, Elena
AU  - Burillo E
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Tarin, Carlos
AU  - Tarin C
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Torres-Fonseca, Monica-Maria
AU  - Torres-Fonseca MM
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Fernandez-Garcia, Carlos-Ernesto
AU  - Fernandez-Garcia CE
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Martinez-Pinna, Roxana
AU  - Martinez-Pinna R
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Martinez-Lopez, Diego
AU  - Martinez-Lopez D
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Llamas-Granda, Patricia
AU  - Llamas-Granda P
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Camafeita, Emilio
AU  - Camafeita E
AD  - Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones 
      Cardiovasculares (CNIC), Madrid, Spain.
FAU - Lopez, Juan Antonio
AU  - Lopez JA
AD  - Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones 
      Cardiovasculares (CNIC), Madrid, Spain.
FAU - Vega de Ceniga, Melina
AU  - Vega de Ceniga M
AD  - Hospital de Galdakao, Vizcaya, Spain.
FAU - Aviram, Michael
AU  - Aviram M
AD  - The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family 
      Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, 
      Israel.
FAU - Egido, Jesus
AU  - Egido J
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Blanco-Colio, Luis-Miguel
AU  - Blanco-Colio LM
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain.
FAU - Martin-Ventura, Jose-Luis
AU  - Martin-Ventura JL
AD  - Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, 
      Spain jlmartin@fjd.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160318
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
RN  - EC 3.1.8.1 (PON1 protein, human)
RN  - EC 3.1.8.1 (PON1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/*metabolism/prevention & control
MH  - Apoptosis/drug effects
MH  - Aryldialkylphosphatase/*metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Humans
MH  - Inflammation/metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Proteomics/methods
OTO - NOTNLM
OT  - abdominal aortic aneurysm
OT  - immune-inflammatory response
OT  - oxidative stress
OT  - paraoxonase-1
OT  - proteomics
EDAT- 2016/03/20 06:00
MHDA- 2017/04/12 06:00
CRDT- 2016/03/20 06:00
PHST- 2016/01/08 00:00 [received]
PHST- 2016/03/16 00:00 [accepted]
PHST- 2016/03/20 06:00 [entrez]
PHST- 2016/03/20 06:00 [pubmed]
PHST- 2017/04/12 06:00 [medline]
AID - CS20160185 [pii]
AID - 10.1042/CS20160185 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2016 Jun 1;130(12):1027-38. doi: 10.1042/CS20160185. Epub 2016 
      Mar 18.