Faculty Collaboration Database

Modification of HDL by reactive aldehydes alters select cardioprotective functions of HDL in macrophages. FEBS J 2020 Feb;287(4):695-707

Date

08/07/2019

Pubmed ID

31386799

Pubmed Central ID

PMC7002295

DOI

10.1111/febs.15034

Scopus ID

2-s2.0-85070750063 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

While increased levels of high-density lipoprotein (HDL)-cholesterol correlate with protection against cardiovascular disease, recent findings demonstrate that HDL function, rather than HDL-cholesterol levels, may be a better indicator of cardiovascular risk. One mechanism by which HDL function can be compromised is through modification by reactive aldehydes such as acrolein (Acro), 4-hydroxynonenal, and malondialdehyde (MDA). In this study, we tested the hypothesis that modification of HDL with reactive aldehydes would impair HDL's athero-protective functions in macrophages. Compared to native HDL, Acro- and MDA-modified HDL have impaired abilities to promote migration of primary peritoneal macrophages isolated from C57BL6/J mice. Incubation of macrophages with MDA-HDL also led to an increased ability to generate reactive oxygen species. Our studies revealed that the changes in HDL function following aldehyde modification are likely not through activation of canonical nuclear factor-kappa B signaling pathways. Consistent with this finding, treatment of either noncholesterol-loaded macrophages or foam cells with modified forms of HDL does not lead to significant changes in expression levels of inflammatory markers. Importantly, our data also demonstrate that changes in HDL function are dependent on the type of modification present on the HDL particle. Our findings suggest that modification of HDL with reactive aldehydes can impair some, but not all, of HDL's athero-protective functions in macrophages.

Author List

Schill RL, Knaack DA, Powers HR, Chen Y, Yang M, Schill DJ, Silverstein RL, Sahoo D

Authors

Yiliang Chen PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Daisy Sahoo PhD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin
Roy L. Silverstein MD Chair, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acrolein
Aldehydes
Animals
Cell Movement
Female
Gene Expression
Interleukin-10
Interleukin-1beta
Interleukin-6
Lipoproteins, HDL
Lipoproteins, LDL
Macrophages, Peritoneal
Male
Malondialdehyde
Mice
Mice, Inbred C57BL
NF-kappa B
Nitric Oxide Synthase Type II
Primary Cell Culture
Reactive Oxygen Species
Tumor Necrosis Factor-alpha