27ca57b30ce5c1ae92836e35a045a391 pmc_33233455.pdf f213aa3e23f6b6dd0ab57ad20827821078e247ef pmc_33233455.pdf 926faac10ac4f454cbb36bcbe00aa7e3c95fc2fbf9be556794026f5bf24e62ee pmc_33233455.pdf Title: Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice Subject: The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNF (NAM LD: -44%; NAM HD: -57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation. Keywords: macrophage; cytokine; ATP-binding cassette (ABC) transporters; niacinamide; vitamin B3; cardiovascular disease Author: Karen Alejandra Méndez-Lara, Nicole Letelier, Nuria Farre, Elena M. G. Diarte-Añazco, Núria Nieto-Nicolau, Elisabeth Rodríguez-Millán, David Santos, Victor Pallarès, Joan Carles Escolà-Gil, Tania Vázquez del Olmo, Enrique Lerma, Mercedes Camacho, Ricardo P Casaroli-Marano, Annabel F. Valledor, Francisco Blanco-Vaca and Josep Julve Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Mon Nov 23 06:41:21 2020 CET ModDate: Mon Nov 23 06:54:10 2020 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4671611 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BWOCSI+Pxsy Type 1 Builtin yes yes no 10 0 MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 14 0 IPQNQD+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 WOVIQI+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 KDFGVP+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 IELMKZ+Rpxr Type 1 Builtin yes yes no 32 0 NXQZWG+EURM10 Type 1 Builtin yes yes no 36 0 CKNIOL+VnURWPalladioL-Bold Type 1 Custom yes yes no 40 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 70 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 74 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 78 0 GBLQZB+Rpxi Type 1 Builtin yes yes no 88 0 YICMPF+Rpcxr Type 1 Builtin yes yes no 92 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 99 0 FNTSBS+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 108 0 FNTSBS+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 114 0 FNTSBS+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 120 0 FNTSBS+TimesNewRomanPSMT CID TrueType Identity-H yes yes yes 126 0 FNTSBS+ArialMT CID TrueType Identity-H yes yes yes 132 0 FNTSBS+SymbolMT CID TrueType Identity-H yes yes yes 138 0 FNTSBS+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 183 0 FNTSBS+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 189 0 FNTSBS+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 195 0 FNTSBS+TimesNewRomanPSMT CID TrueType Identity-H yes yes yes 201 0 FNTSBS+ArialMT CID TrueType Identity-H yes yes yes 207 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 272 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 276 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 280 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 284 0 Times New Roman TrueType WinAnsi no no no 291 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 04:17:34 CEST RepresentationInformation: pmc_33233455.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 11:43:34 CEST Size: 4671611 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 537 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Item: Title: Results Destination: section.3 Children: Item: Title: Effect of NAM on Gross Parameters and Systemic Phenotype Destination: subsection.3.1 Item: Title: NAM Administration Prevents the Development of Aortic Atherosclerosis Destination: subsection.3.2 Item: Title: NAM Administration Directly Protects against the Oxidation of Non-HDL Lipoproteins Destination: subsection.3.3 Item: Title: The NAM Treatment Improves Plasma and Aortic Inflammation Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice Author: Karen Alejandra Méndez-Lara, Nicole Letelier, Nuria Farre, Elena M. G. Diarte-Añazco, Núria Nieto-Nicolau, Elisabeth Rodríguez-Millán, David Santos, Victor Pallarès, Joan Carles Escolà-Gil, Tania Vázquez del Olmo, Enrique Lerma, Mercedes Camacho, Ricardo P Casaroli-Marano, Annabel F. Valledor, Francisco Blanco-Vaca and Josep Julve Subject: The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNF (NAM LD: -44%; NAM HD: -57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation. 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