Overexpression of angiopoietin-like protein 4 protects against atherosclerosis development.
Arterioscler Thromb Vasc Biol
; 33(7): 1529-37, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23640487
ABSTRACT
OBJECTIVE:
Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized the regulation of Angptl4 expression in macrophages and examined the impact of Angptl4 on atherosclerosis development. APPROACH ANDRESULTS:
Macrophage activation elicited by pathogen-recognition receptor agonists decreased Angptl4 expression, whereas lipid loading by intralipid and oxidized low-density lipoprotein increased Angptl4 expression. Consistent with an antilipotoxic role of Angptl4, recombinant Angptl4 significantly decreased uptake of oxidized low-density lipoprotein by macrophages, via lipolysis-dependent and -independent mechanisms. Angptl4 protein was detectable in human atherosclerotic lesions and localized to macrophages. Transgenic overexpression of Angptl4 in atherosclerosis-prone apolipoprotein E*3-Leiden mice did not significantly alter plasma cholesterol and triglyceride levels. Nevertheless, Angptl4 overexpression reduced lesion area by 34% (P<0.05). In addition, Angptl4 overexpression decreased macrophage content (-41%; P<0.05) and numbers of monocytes adhering to the endothelium wall (-37%; P<0.01). Finally, plasma Angptl4 was independently and negatively associated with carotid artery sclerosis measured by 3-T MRI in subjects with metabolic syndrome and low-grade systemic inflammation.CONCLUSIONS:
Angptl4 suppresses foam cell formation to reduce atherosclerosis development. Stimulation of Angptl4 in macrophages by oxidized low-density lipoprotein may protect against lipid overload.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças da Aorta
/
Estenose das Carótidas
/
Angiopoietinas
/
Aterosclerose
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article