In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. suppl_1 ( 2015-05)
Abstract:
Adipose tissue inflammation associates with insulin resistance and increased cardiovascular disease risk. HDL has both anti-inflammatory and atheroprotective properties. We recently showed that HDL from healthy humans and lean mice inhibits palmitate-induced monocyte chemotactic factor expression by decreasing lipid raft (LR) content in adipocytes. However, little is known regarding whether inflammation would cause HDL to lose these anti-inflammatory effects on adipocytes. To generate HDL under conditions of sterile inflammation, HDL was purified from plasma of AgNO 3 -injected C57BL/6 mice. In 3T3L-1 adipocytes, “inflamed HDL” did not disrupt the formation of LR or inhibit monocyte chemotactic factor expression. Moreover, inflamed HDL lost its ability to facilitate cholesterol efflux in adipocytes. To determine causal factors of HDL that might be responsible for this loss of anti-inflammatory effect on adipocytes, we investigated role of serum amyloid A (SAA), levels of which are increased up to 1000 fold in HDL by acute inflammation. In a loss of function study, inflamed HDL from AgNO 3 -injectd SAA1/2 double knockout (DKO) mice restored part of its anti-inflammatory and cholesterol efflux capacity. Conversely, in a gain of function study, increasing the SAA content in uninflamed HDL by exposure to 293 HEK cells with lentiviral overexpression of SAA2 resulted in a partial loss of its anti-inflammatory effect and cholesterol efflux capacity. To determine whether HDL from moderately inflamed humans had similar effects on adipocyte inflammation, HDL isolated from patients with systemic lupus erythematosus (n=18) also demonstrated impaired anti-inflammatory effects in adipocytes. The extent of impairment associated positively with plasma SAA levels ( r =0.80; p 〈 0.001), and negatively with cholesterol efflux capacity of the HDL ( r =-0.74; p 〈 0.001). These findings indicate that inflamed HDL loses its anti-inflammatory effect and cholesterol efflux capacity on adipocytes. The presence of SAA in HDL may contribute to the generation of dysfunctional HDL and should be considered as a causal factor, not simply as a biomarker of dysfunctional HDL.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.35.suppl_1.114
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1494427-3
