Imikhiqizo

I-Niacin (i-nicotinic acid) njenge-monotherapy inganciphisa ingozi yesifo se-vascular, kodwa indlela yokusebenza kwayo ihlala iyimpikiswano, futhi ingase inganciki emiphumeleni ye-systemic lipid yokuguqula.I-Niacin isanda kuboniswa ukuthuthukisa umsebenzi we-endothelial kanye nokuvuselelwa kwe-vascular, ngaphandle kokulungisa i-dyslipidemia, kumamodeli wamagundane okulimala kwe-vascular kanye nesifo se-metabolic.Njengesandulela se-biosynthetic esingaba khona se-NAD(+), i-niacin ingathola lezi zinzuzo ze-vascular ngokusebenzisa izimpendulo ezincike ku-NAD(+), ezincike ku-sirtuin (SIRT).Kungenjalo, i-niacin ingase isebenze ngesamukeli sayo, i-GPR109A, ukukhuthaza ukusebenza kwe-endothelial, nakuba amaseli e-endothelial engaziwa ukuthi aveze lesi samukeli.Sacabanga ukuthi i-niacin ithuthukisa ngokuqondile ukusebenza kweseli endothelial ngesikhathi sokuchayeka ezimweni ze-lipotoxic futhi safuna ukunquma indlela/izindlela ezingaba khona ezihilelekile.Ukusebenza kwe-angiogenic ku-palmitate eyeqile kwahlolwa ngokwakhiwa kweshubhu kulandela ukwelashwa kwamangqamuzana e-microvascular endothelial (HMVE C) noma ukuhlushwa okuphansi kakhulu kwe-niacin (10 μM), noma i-nicotinamide mononucleotide (NMN) (1 μM), isandulela se-NAD(+) esiqondile.Nakuba kokubili i-niacin ne-NMN kuthuthukise ukwakheka kweshubhu le-HMVEC phakathi nokugcwala kwe-palmitate, i-NMN kuphela ekhuphule i-NAD(+) yeselula kanye nomsebenzi we-SIRT1.Siphinde saqaphela ukuthi i-HMVEC iveza i-GRP109A.Ukwenza kusebenze lesi samukeli esine-acifran noma i-MK-1903 eyenziwe kabusha ngokuthuthukiswa kwe-niacin ekwakhekeni kweshubhu le-HMVEC, kuyilapho i-GPR109A siRNA yehlisa umphumela we-niacin.Niacin, ekugxiliseni okuphansi, kuthuthukisa ukusebenza kwe-HMVEC angiogenic ngaphansi kwezimo ze-lipotoxic, cishe ezizimele ku-NAD( +) i-biosynthesis kanye nokwenza kusebenze kwe-SIRT1, kodwa kunalokho ngokusebenzisa i-niacin receptor activation.