Journal article
Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity
Nutrients, Vol.12(7), pp.1937-19
06/30/2020
DOI: 10.3390/nu12071937
PMCID: PMC7400685
PMID: 32629758
Abstract
Atheroprotective functions of high-density lipoproteins (HDL) are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished, and MDA-HDL adduct levels were decreased. PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL from
Apoe
−/−
macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity. MDA modification of HDL reduced its anti-inflammatory function compared to native HDL. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and PON1 activity was also impaired in FH. Consistently, FH-HDL induced a pro-inflammatory response in
Apoe
−/−
macrophages and had an impaired ability to promote cholesterol efflux. Interestingly, reactive dicarbonyl scavengers, including 2-hydroxybenzylamine (2-HOBA) and pentyl-pyridoxamine (PPM), effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers reduced MDA-HDL adduct formation and increased HDL cholesterol efflux capacity, supporting the therapeutic potential of reactive carbonyl scavenging for improving HDL function.
Details
- Title: Subtitle
- Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity
- Creators
- Jiansheng Huang - Vanderbilt University Medical CenterPatricia G. Yancey - Vanderbilt University Medical CenterHuan TaoMark S. Borja - California State University, East BayLoren E. Smith - Vanderbilt University Medical CenterValentina Kon - Vanderbilt University Medical CenterSean S. Davies - Vanderbilt UniversityMacRae F. Linton - Vanderbilt University Medical Center
- Resource Type
- Journal article
- Publication Details
- Nutrients, Vol.12(7), pp.1937-19
- DOI
- 10.3390/nu12071937
- PMID
- 32629758
- PMCID
- PMC7400685
- NLM abbreviation
- Nutrients
- ISSN
- 2072-6643
- eISSN
- 2072-6643
- Publisher
- MDPI
- Language
- English
- Date published
- 06/30/2020
- Academic Unit
- Anesthesia
- Record Identifier
- 9984949263402771
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