Antiatherosclerotic effects of 1-methylnicotinamide in apolipoprotein E/low-density lipoprotein receptor-deficient mice : a comparison with nicotinic acid

2016
journal article
article
34
cris.lastimport.wos2024-04-09T18:38:00Z
dc.abstract.en1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/ low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/ LDLR2/2 mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F1a and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR2/2 mice, an effect associated with an improvement in prostacyclin- and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA.pl
dc.affiliationWydział Lekarski : Zakład Farmakologiipl
dc.affiliationPion Rektora : Jagiellońskie Centrum Rozwoju Lekówpl
dc.affiliationWydział Farmaceutyczny : Zakład Toksykologiipl
dc.affiliationWydział Chemii : Zakład Fizyki Chemicznejpl
dc.cm.id74832
dc.contributor.authorMateuszuk, Łukasz - 159343 pl
dc.contributor.authorJasztal, Agnieszka - 129875 pl
dc.contributor.authorMaślak, Edyta - 211387 pl
dc.contributor.authorGąsior-Głogowska, Marlena - 243460 pl
dc.contributor.authorBarańska, Małgorzata - 127224 pl
dc.contributor.authorSitek, Barbara - 200898 pl
dc.contributor.authorKostogrys, Renata - 102696 pl
dc.contributor.authorZakrzewska, Agnieszka - 198214 pl
dc.contributor.authorKij, Agnieszka - 215016 pl
dc.contributor.authorWalczak, Maria - 133728 pl
dc.contributor.authorChłopicki, Stefan - 128995 pl
dc.date.accessioned2016-08-22T08:11:30Z
dc.date.available2016-08-22T08:11:30Z
dc.date.issued2016pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number2pl
dc.description.physical514-524pl
dc.description.points35pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume356pl
dc.identifier.doi10.1124/jpet.115.228643pl
dc.identifier.eissn1521-0103pl
dc.identifier.issn0022-3565pl
dc.identifier.urihttp://ruj.uj.edu.pl/xmlui/handle/item/29750
dc.languageengpl
dc.language.containerengpl
dc.rightsDodaję tylko opis bibliograficzny*
dc.rights.licenceOTHER
dc.rights.uri*
dc.share.typeinne
dc.subtypeArticlepl
dc.titleAntiatherosclerotic effects of 1-methylnicotinamide in apolipoprotein E/low-density lipoprotein receptor-deficient mice : a comparison with nicotinic acidpl
dc.title.journalThe Journal of Pharmacology and Experimental Therapeuticspl
dc.typeJournalArticlepl
dspace.entity.typePublication
cris.lastimport.wos
2024-04-09T18:38:00Z
dc.abstract.enpl
1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/ low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/ LDLR2/2 mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F1a and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR2/2 mice, an effect associated with an improvement in prostacyclin- and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA.
dc.affiliationpl
Wydział Lekarski : Zakład Farmakologii
dc.affiliationpl
Pion Rektora : Jagiellońskie Centrum Rozwoju Leków
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Toksykologii
dc.affiliationpl
Wydział Chemii : Zakład Fizyki Chemicznej
dc.cm.id
74832
dc.contributor.authorpl
Mateuszuk, Łukasz - 159343
dc.contributor.authorpl
Jasztal, Agnieszka - 129875
dc.contributor.authorpl
Maślak, Edyta - 211387
dc.contributor.authorpl
Gąsior-Głogowska, Marlena - 243460
dc.contributor.authorpl
Barańska, Małgorzata - 127224
dc.contributor.authorpl
Sitek, Barbara - 200898
dc.contributor.authorpl
Kostogrys, Renata - 102696
dc.contributor.authorpl
Zakrzewska, Agnieszka - 198214
dc.contributor.authorpl
Kij, Agnieszka - 215016
dc.contributor.authorpl
Walczak, Maria - 133728
dc.contributor.authorpl
Chłopicki, Stefan - 128995
dc.date.accessioned
2016-08-22T08:11:30Z
dc.date.available
2016-08-22T08:11:30Z
dc.date.issuedpl
2016
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
2
dc.description.physicalpl
514-524
dc.description.pointspl
35
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
356
dc.identifier.doipl
10.1124/jpet.115.228643
dc.identifier.eissnpl
1521-0103
dc.identifier.issnpl
0022-3565
dc.identifier.uri
http://ruj.uj.edu.pl/xmlui/handle/item/29750
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Dodaję tylko opis bibliograficzny
dc.rights.licence
OTHER
dc.rights.uri*
dc.share.type
inne
dc.subtypepl
Article
dc.titlepl
Antiatherosclerotic effects of 1-methylnicotinamide in apolipoprotein E/low-density lipoprotein receptor-deficient mice : a comparison with nicotinic acid
dc.title.journalpl
The Journal of Pharmacology and Experimental Therapeutics
dc.typepl
JournalArticle
dspace.entity.type
Publication

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