Niacin action in the atherogenic mixed dyslipidemia of metabolic syndrome: Insights from metabolic biomarker profiling and network analysis.

Autor:	Adiels, Martin, Chapman, M. John, Robillard, Paul, Krempf, Michel, Laville, Martine, Borén, Jan
Předmět:	CELL proliferation APOLIPOPROTEINS BIOMARKERS BIOLOGICAL assay C-reactive protein CELL adhesion molecules ENZYME-linked immunosorbent assay HIGH density lipoproteins HOMEOSTASIS HYPERLIPIDEMIA INFLAMMATORY mediators INSULIN resistance INTERLEUKINS LIPIDS LIVER LOW density lipoproteins MACROPHAGES NIACIN OBESITY PROTEOLYTIC enzymes STATISTICS TRIGLYCERIDES TUMOR necrosis factors HOMOCYSTEINE PHENOTYPES BIOCHIPS METABOLIC syndrome CYSTATINS ADIPONECTIN GAMMA-glutamyltransferase PHARMACODYNAMICS
Zdroj:	Journal of Clinical Lipidology; May2018, Vol. 12 Issue 3, p810-821.e1, 1p
Abstrakt:	Background Niacin as an adjunct to statin treatment to reduce cardiovascular risk is questioned. Objective To evaluate interrelationships between the effects of niacin on mixed dyslipidemia and a spectrum of metabolic and inflammatory biomarkers. Methods Obese, nondiabetic, hypertriglyceridemic males ( n = 19) with low high-density lipoprotein–cholesterol levels received extended-release nicotinic acid for 8 weeks. Multiple biomarkers were measured using enzyme-linked immunosorbent assay, enzymatic/absorptiometric, or multiplex biochip assays. Treatment effects were determined for each variable and a differential correlation network created on the basis of univariate correlations between baseline and response to niacin treatment for all pairs of variables. Results Extended-release niacin treatment favoured normalization of plasma lipid and apolipoprotein profile. Plasma markers of inflammation, hepatic function, cellular adhesion and proliferation, and macrophage phenotype were attenuated; however, insulin resistance increased. Differential network analysis revealed that changes in triglycerides and high-density lipoprotein–cholesterol were closely linked; equally, niacin mediated reductions in total cholesterol, apolipoprotein B, low-density lipoprotein–cholesterol and lipoprotein(a) clustered together, as did homeostatic model assessment of insulin resistance, insulin, and interleukin-6 levels. Two clusters of inflammatory markers were identified, involving (1) intercellular adhesion molecule 1 and high-sensitive C-reactive protein and (2) soluble tumor necrosis factor receptors; and novel clusters involving matrix metallopeptidase 9 and apolipoprotein E, and adiponectin and cystatin C, respectively, were equally revealed. At lower stringency, lipid and insulin resistance clusters were linked; a C-reactive protein-centered cluster linked reduction in apolipoprotein CIII to intercellular adhesion molecule 1, gamma-glutamyltransferase, soluble tumor necrosis factor receptors, and E-selectin. Conclusion A niacin-mediated trend to normalize atherogenic mixed dyslipidemia was intimately linked to attenuation of biomarkers of inflammation, cell adhesion, hepatic dysfunction and cell proliferation, but to enhanced insulin resistance and plasma homocysteine elevation. [ABSTRACT FROM AUTHOR]
Databáze:	Supplemental Index
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