Human apolipoprotein A-IV reduces secretion of proinflammatory cytokines and atherosclerotic effects of a chronic infection mimicked by lipopolysaccharide.

Abstract

OBJECTIVE:

Expression of human apolipoprotein (h-apo) A-IV in apoE-deficient (apoE(0)) mice (h-apoA-IV/E(0)) reduces susceptibility to atherosclerosis. Chronic infection mimicked by exposure to lipopolysaccharide (LPS) increases the size of atherosclerosis lesions in apoE(0) mice. Thus, we used h-apoA-IV/E(0) mice to determine whether h-apoA-IV plays a protective role after LPS administration.

METHODS AND RESULTS:

We injected apoE(0), h-apoA-IV/E(0), and C57Bl/6 (wild-type) mice intraperitoneally with either LPS or phosphate-buffered saline (PBS) every week for 10 weeks. Atherosclerotic lesions were significantly smaller in h-apoA-IV/E(0) mice treated with LPS than in their apoE(0) counterparts. The titers of IgG2a and IgG2b autoantibodies to oxidized low-density lipoprotein (LDL) were higher in the LPS-group of h-apoA-IV/E(0) mice than in apoE(0) mice, suggesting that the Th1 response is stronger in the presence of h-apoA-IV. Lymphocytes from the blood, liver, spleen, and thymus of h-apoA-IV/E(0) mice treated with LPS produced less IL-4, INF-gamma, and TNF-alpha proinflammatory cytokines than their apoE(0) counterparts. Furthermore, we demonstrated that recombinant h-apoA-IV blocks the LPS-induced stimulation of monocytes.

CONCLUSIONS:

The expression of h-apoA-IV in apoE(0) mice reduces the susceptibility to atherogenesis and decreases the secretion of proinflammatory cytokines after LPS administration.

• Authors: Delia Recalde, Maria A Ostos, Edgar Badell, Angel-Luis Garcia-Otin, Josette Pidoux, Graciela Castro, Mario M Zakin, Daniel Scott-Algara
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 4 Pg. 756-61 (Apr 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 14751811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins A
• Apolipoproteins E
• Autoantibodies
• Cytokines
• Lipids
• Lipopolysaccharides
• Lipoproteins, LDL
• Recombinant Fusion Proteins
• apolipoprotein A-IV
• oxidized low density lipoprotein

Topics

• Animals
• Apolipoproteins A (genetics, physiology)
• Apolipoproteins E (deficiency, genetics)
• Arteriosclerosis (blood, genetics, pathology, prevention & control)
• Autoantibodies (blood, immunology)
• Blood Cells (metabolism)
• Cytokines (biosynthesis, metabolism)
• Humans
• Infections
• Lipids (blood)
• Lipopolysaccharides (pharmacology, toxicity)
• Lipoproteins, LDL (immunology)
• Liver (metabolism, pathology)
• Lymphocyte Subsets (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Animal
• Monocytes (drug effects, physiology)
• Recombinant Fusion Proteins (physiology)
• Spleen (metabolism, pathology)
• Thymus Gland (metabolism, pathology)