Chronic LPSF/GQ-02 treatment attenuates inflammation and atherosclerosis development in LDLr-/-mice.
BACKGROUND
Atherosclerosis is a complex disorder with a multifactorial pathogenesis. We previously indicated that the new TZD LPSF/GQ-02 inhibits hepatic steatosis and inflammation, which are reported as risk factors for atherosclerosis development. Here, we explored the effects of LPSF/GQ-02 on atherosclerosis in LDLr-/- mice comparing two treatment periods.


RESULTS
LDLr-/-mice were fed a high-fat diet for 10 and 12 weeks and received oral treatment with LPSF/GQ-02 (30mg/kg/day) or pioglitazone (20mg/kg/day) for 15 and 30 days, respectively. Both treatment protocols with LPSF/GQ-02 resulted in lower collagen density in the atherosclerotic lesions. In addition, the treatment for 15 days also decreased mRNA levels of CD40, MCP-1, ABCG1 and upregulated PPARα, whereas the 30-days treatment reduced the protein levels of LOX-1, p-IκBα and p-NFκB.


CONCLUSIONS
This study provides evidence that LPSF/GQ-02 affects the composition and growth of atherosclerotic lesions in LDLr-/-mice. Moreover, our data also support previous findings showing anti-inflammatory properties of LPSF/GQ-02 and reinforce the therapeutic potential of this TZD for treating atherosclerosis and inflammation-related disorders.
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil; Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil.
Amanda Karolina Soares E
AKSE
Silva
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil; Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil.
Fabiana Oliveira Dos Santos
FODS
Gomes
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil; Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil.
Bruna Dos
BD
Santos Silva
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil; Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil.
Edlene Lima
EL
Ribeiro
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil; Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil.
Amanda Costa
AC
Oliveira
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil; Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil.
Shyrlene Meyre da Rocha
SMDR
Araújo
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil; Universidade Federal de Pernambuco, Recife, Pernambuco, Brasil.
Ingrid Tavares
IT
de Lima
Centro de Tecnologias Estratégicas do Nordeste (CETENE), Recife, Pernambuco, Brasil.
Anne Gabrielle Vasconcelos
AGV
Oliveira
Departmento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brasil.
Martina
M
Rudnicki
Departmento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brasil.
Dulcineia S P
DSP
Abdalla
Laboratório de Planejamento e Síntese de Fármacos, Universidade Federal de Pernambuco, Recife, Brasil.
Maria do Carmo Alves de
MDCA
Lima
Laboratório de Planejamento e Síntese de Fármacos, Universidade Federal de Pernambuco, Recife, Brasil.
Ivan da Rocha
IDR
Pitta
Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, Pernambuco, Brasil. Electronic address: peixoto.christina@gmail.com.
Christina Alves
CA
Peixoto
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D000071518:Liver X Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency*; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
C581247:5-(4-chlorobenzylidene)-3-(4-methylbenzyl)thiazolidine-2,4-dione; D000893:Anti-Inflammatory Agents; D000071518:Liver X Receptors; D047493:PPAR alpha; D047495:PPAR gamma; D011973:Receptors, LDL; D045162:Thiazolidinediones; D003094:Collagen; D002784:Cholesterol
Atherosclerosis; Inflammation; LPSF/GQ-02; Thiazolidinediones