Serum amyloid A impairs the antiinflammatory properties of HDL

Chang Yeop Han, Chongren Tang, Myriam E. Guevara, Hao Wei, Tomasz Wietecha, Baohai Shao, Savitha Subramanian, Mohamed Omer, Shari Wang, Kevin D. O'Brien, Santica M. Marcovina, Thomas N. Wight, Tomas Vaisar, Maria C. De Beer, Frederick C. De Beer, William R. Osborne, Keith B. Elkon, Alan Chait

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgNO3 fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgNO3-injected mice lacking Saa1.1 and Saa2.1 exhibited a partial restoration of antiinflammatory and cholesterol efflux properties in adipocytes. Conversely, incorporation of SAA into HDL preparations reduced antiinflammatory properties but not to the same extent as HDL from AgNO3-injected mice. SAAenriched HDL colocalized with cell surface-associated extracellular matrix (ECM) of adipocytes, suggesting impaired access to the plasma membrane. Enzymatic digestion of proteoglycans in the ECM restored the ability of SAA-containing HDL to inhibit palmitate-induced inflammation and cholesterol efflux. Collectively, these findings indicate that inflammation results in a loss of the antiinflammatory properties of HDL on adipocytes, which appears to partially result from the SAA component of HDL binding to cell-surface proteoglycans, thereby preventing access of HDL to the plasma membrane.

Original languageEnglish
Pages (from-to)266-281
Number of pages16
JournalJournal of Clinical Investigation
Volume126
Issue number1
DOIs
StatePublished - Jan 4 2016

Bibliographical note

Funding Information:
C. Tang and S. Wang have equity in health care–related publicly traded companies. K.D. O’Brien has received a grant from Sanofi. S.M. Marcovina is a consultant to Denka, Japan, and Medtest, USA; holds a patent for an assay for lipoprotein(a); and has received a grant from Inventive Health Clinical LLC. F.C. de Beer is an inventor and holds a patent entitled “Compositions and methods for detecting and treating atherosclerosis.” K.B. Elkon has part ownership of a company called Resolve Therapeutics LLC. This work was supported in part by NIH grants HL092969, 094352, and DK-035816 and a Beginning Grant-in-Aid from the American Heart Association (to C.Y. Han). A. Chait was supported by a Grant-in-Aid from the American Heart Association.

Funding Information:
C. Tang and S. Wang have equity in health care?related publicly traded companies. K.D. O?Brien has received a grant from Sanofi. S.M. Marcovina is a consultant to Denka, Japan, and Medtest, USA; holds a patent for an assay for lipoprotein(a); and has received a grant from Inventive Health Clinical LLC. F.C. de Beer is an inventor and holds a patent entitled ?Compositions and methods for detecting and treating atherosclerosis.? K.B. Elkon has part ownership of a company called Resolve Therapeutics LLC. This work was supported in part by NIH grants HL092969, 094352, and DK-035816 and a Beginning Grant-in-Aid from the American Heart Association (to C.Y. Han). A. Chait was supported by a Grant-in-Aid from the American Heart Association.

ASJC Scopus subject areas

  • General Medicine

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