Publication year
2013Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 33, 7, (2013), pp. 1529-1537ISSN
Publication type
Article / Letter to editor
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Organization
Internal Medicine
Surgery
Journal title
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
vol. 33
Issue
iss. 7
Page start
p. 1529
Page end
p. 1537
Subject
IGMD 5: Health aging / healthy living; IGMD 5: Health aging / healthy living NCEBP 14: Cardiovascular diseases; NCEBP 14: Cardiovascular diseases; NCEBP 14: Cardiovascular diseases NCMLS 3: Tissue engineering and pathologyAbstract
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 AND RESULTS: 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.
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- Academic publications [238441]
- Faculty of Medical Sciences [90373]
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