PMID- 25869519
OWN - NLM
STAT- MEDLINE
DCOM- 20160513
LR  - 20150803
IS  - 1879-3649 (Electronic)
IS  - 1537-1891 (Linking)
VI  - 71
DP  - 2015 Aug
TI  - New indole-thiazolidine attenuates atherosclerosis in LDLr(-/-) mice.
PG  - 174-80
LID - S1537-1891(15)00048-8 [pii]
LID - 10.1016/j.vph.2015.03.009 [doi]
AB  - Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma 
      (PPARgamma) agonists that improve insulin-mediated glucose uptake and possess 
      beneficial vasculoprotective actions. However, because undesirable side effects 
      are associated with these drugs, novel TZDs are under development. In this study, 
      we evaluated the biological activity of LYSO-7, a new indole-thiazolidine, on 
      PPAR activation, inflammation and atherogenesis using a gene reporter assay, 
      lipopolysaccharide (LPS)-activated RAW 264.7 cell culture, and a low-density 
      lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis. LYSO-7 
      shows low cytotoxicity in RAW 264.7 cells and at 2.5mumol/L induces PPARalpha and 
      PPARgamma transactivation as well as inhibits LPS-induced nitrite production and the 
      mRNA gene expression levels of inducible nitric oxide synthase (iNOS), 
      cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1) and monocyte 
      chemoattractant protein-1 (MCP-1). In addition, treatment with LYSO-7 reduces the 
      development of atherosclerosis in LDLr(-/-) mice, improves the lipid profile, 
      blood glucose levels, and downregulates CD40 and CD40L expression without 
      affecting the body weight of the animals. Altogether, our data show that LYSO-7 
      possesses anti-inflammatory properties and that treatment with this TZD 
      attenuates atherosclerosis progression in LDLr(-/-) mice by modulating lipid 
      metabolism and inflammation. Thus, LYSO-7 shows potential as a new drug candidate 
      for the treatment of atherosclerosis.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Cesar, Fernanda A
AU  - Cesar FA
AD  - Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
FAU - Rudnicki, Martina
AU  - Rudnicki M
AD  - Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
FAU - de Las Heras, Beatriz
AU  - de Las Heras B
AD  - Department of Pharmacology, Faculty of Pharmacy, Complutense University of 
      Madrid, Madrid, Spain.
FAU - Bosca, Lisardo
AU  - Bosca L
AD  - Instituto de Investigaciones Biomedicas Alberto Sols (CSIC-UAM), Madrid, Spain.
FAU - Lima, Maria C A
AU  - Lima MC
AD  - Center of Health Sciences, Federal University of Pernambuco, Recife, PE, Brazil.
FAU - Pitta, Ivan R
AU  - Pitta IR
AD  - Center of Health Sciences, Federal University of Pernambuco, Recife, PE, Brazil.
FAU - Abdalla, Dulcineia S P
AU  - Abdalla DS
AD  - Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: 
      dspa@usp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150411
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 (5-((5-bromo-1H-indol-3-yl)methylene)-3-(4-chlorobenzyl)thiazolidine-2,4-dione)
RN  - 0 (Indoles)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Receptors, LDL)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Thiazolidines)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*metabolism/*prevention & control
MH  - Cell Line
MH  - Indoles/pharmacology/*therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Peroxisome Proliferator-Activated Receptors/agonists
MH  - Receptors, LDL/*deficiency
MH  - Thiazolidinediones/pharmacology/*therapeutic use
MH  - Thiazolidines/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - Anti-inflammatory
OT  - Atherosclerosis
OT  - LYSO-7
OT  - Thiazolidinediones
EDAT- 2015/04/15 06:00
MHDA- 2016/05/14 06:00
CRDT- 2015/04/15 06:00
PHST- 2014/11/25 00:00 [received]
PHST- 2015/03/02 00:00 [revised]
PHST- 2015/03/28 00:00 [accepted]
PHST- 2015/04/15 06:00 [entrez]
PHST- 2015/04/15 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
AID - S1537-1891(15)00048-8 [pii]
AID - 10.1016/j.vph.2015.03.009 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2015 Aug;71:174-80. doi: 10.1016/j.vph.2015.03.009. Epub 2015 
      Apr 11.