Iimveliso

I-Niacin (i-nicotinic acid) njenge-monotherapy inokunciphisa umngcipheko wesifo se-vascular, kodwa indlela yokusebenza kwayo ihlala iphikisana, kwaye ayinakuxhomekeka kwimiphumo yokuguqula i-lipid.I-Niacin isanda kuboniswa ukuphucula umsebenzi we-endothelial kunye nokuvuselelwa kwe-vascular, ezimeleyo ekulungiseni i-dyslipidemia, kwiimodeli ze-rodent zokulimala kwe-vascular kunye nesifo se-metabolic.Njengesandulela se-biosynthetic esinokubakho se-NAD (+), i-niacin inokufumana ezi zibonelelo ze-vascular ngokusebenzisa i-NAD (+)-exhomekeke, i-sirtuin (SIRT) iimpendulo ezidibeneyo.Ngaphandle koko, i-niacin inokusebenza nge-receptor yayo, i-GPR109A, ukukhuthaza umsebenzi we-endothelial, nangona iiseli ze-endothelial zingaziwa ukuba zivakalise le receptor.Sacinga ukuba i-niacin iphucula ngokuthe ngqo ukusebenza kweeseli ze-endothelial ngexesha lokuvezwa kweemeko ze-lipotoxic kwaye safuna ukufumanisa indlela (s) enokuthi ibandakanyeke. Umsebenzi we-Angiogenic kwi-palmitate engaphezulu kwavavanywa ngokubunjwa kwetyhubhu emva kokunyangwa kweeseli ze-microvascular endothelial (HMVE C) nokuba Uxinzelelo oluphantsi ngokwentelekiso lwe-niacin (10 μM), okanye i-nicotinamide mononucleotide (NMN) (1 μM), i-NAD ngqo (+) isandulela.Nangona zombini i-niacin kunye ne-NMN ziphucule ukubunjwa kwetyhubhu ye-HMVEC ngexesha lokugqithisa kwe-palmitate, kuphela i-NMN yokwandisa i-NAD yeselula (+) kunye nomsebenzi we-SIRT1.Siphinde saqaphela ukuba i-HMVEC ivakalisa i-GRP109A.Ukusebenzisa le receptor kunye nokuba yi-acifran okanye i-MK-1903 iphinde yaphucula ukuphuculwa kwe-niacin ekubunjweni ityhubhu ye-HMVEC, ngelixa i-GPR109A siRNA iyancipha umphumo we-niacin. +) biosynthesis kunye nokusebenza kwe-SIRT1, kodwa kunokuba kusebenze i-niacin receptor.