Anti-atherogenic effects of methotrexate carried by a lipid nanoemulsion that binds to LDL receptors in cholesterol-fed rabbits.
Cardiovasc Drugs Ther
; 27(6): 531-9, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24065615
ABSTRACT
PURPOSE:
Nanoemulsions (LDE) with a lipid composition resembling that of LDL can concentrate in aortic lesions and when associated with anti-blastic agents, such as paclitaxel or etoposide, decrease atherosclerotic lesions induced in rabbits. Our aim was to test the association of a lipophilic derivative of methotrexate, didodecyl-methotrexate (ddMTX) to LDE on the lesions and on the expression of pro-inflammatory and anti-inflammatory genes.METHODS:
Twenty male New Zealand rabbits were fed 1 % cholesterol diet for 60 days. Starting from day 30, 10 animals were treated with 4 weekly LDE-ddMTX injections (4 mg/kg, I.V.) and 10 with LDE injections (20 mg LDE total lipid mass/kg).RESULTS:
LDE-ddMTX reduced the size of the lesion areas by 65 % and the intima-media ratio by 2-fold. Reduction of intimal macrophage was 67 % and of apoptotic cells was 88 %. Smooth muscle cells migration into the intima was unaffected. LDE-ddMTX treatment diminished metalloproteinase-9 in the intima. In aortas of atherosclerotic rabbits, downregulation of 6 pro-inflammatory genes, TNF-α, MCP-1, IL-1ß, IL-18, MMP-9, MMP-12 and upregulation of the anti-inflammatory IL-10 gene were observed. Incubation of LDE-ddMTX with HUVEC cells led to downregulation of TNF-α IL1-ß VAP-1, TLR2 and CXCL2.CONCLUSIONS:
LDE-ddMTX is potentially useful to threat atherosclerosis by acting on inflammatory processes which are instrumental in the development of the disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Metotrexato
/
Aterosclerose
/
Nanopartículas
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cardiovasc Drugs Ther
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Brasil