Abstract
BACKGROUND: Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL's cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function.
METHODS: A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement.
RESULTS: In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q < 0.01; LDL-C - 20%, q < 0.01; and triglyceride - 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q < 0.05). Niacin did not impact HDL's ability to influence endothelial function.
CONCLUSION: Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.
Document Type
Article
Publication Date
8-21-2020
Digital Object Identifier (DOI)
https://doi.org/10.1186/s12944-020-01350-3
Funding Information
This work was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (ATR).
Related Content
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Repository Citation
Gordon, Scott M.; Amar, Marcelo J.; Jeiran, Kianoush; Stagliano, Michael; Staller, Emma; Playford, Martin P.; Mehta, Nehal N.; Vaisar, Tomas; and Remaley, Alan T., "Effect of Niacin Monotherapy on High Density Lipoprotein Composition and Function" (2020). Saha Cardiovascular Research Center Faculty Publications. 46.
https://uknowledge.uky.edu/cvrc_facpub/46
Additional file 1: Supplementary Table 1. Label-free quantification of HDL-associated proteins.
Notes/Citation Information
Published in Lipids in Health and Disease, v. 19, issue 1, article no. 190.
© The Author(s). 2020
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