Increased atherosclerosis in LDL receptor–null mice lacking ACAT1 in macrophages
AUTOR(ES)
Fazio, Sergio
FONTE
American Society for Clinical Investigation
RESUMO
During atherogenesis, circulating macrophages migrate into the subendothelial space, internalize cholesterol-rich lipoproteins, and become foam cells by progressively accumulating cholesterol esters. The inhibition of macrophage acyl coenzyme A:cholesterol acyltransferase (ACAT), which catalyzes the formation of cholesterol esters, has been proposed as a strategy to reduce foam cell formation and to treat atherosclerosis. We show here, however, that hypercholesterolemic LDL receptor–deficient (LDLR–/–) mice reconstituted with ACAT1-deficient macrophages unexpectedly develop larger atherosclerotic lesions than control LDLR–/– mice. The ACAT1-deficient lesions have reduced macrophage immunostaining and more free cholesterol than control lesions. Our findings suggest that selective inhibition of ACAT1 in lesion macrophages in the setting of hyperlipidemia can lead to the accumulation of free cholesterol in the artery wall, and that this promotes, rather than inhibits, lesion development.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=198874Documentos Relacionados
- Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y1 receptor–null mice
- Naringenin Prevents Dyslipidemia, Apolipoprotein B Overproduction, and Hyperinsulinemia in LDL Receptor–Null Mice With Diet-Induced Insulin Resistance
- Defining thyrotropin-dependent and -independent steps of thyroid hormone synthesis by using thyrotropin receptor-null mice
- Bone homeostasis in growth hormone receptor–null mice is restored by IGF-I but independent of Stat5
- Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages