Kolesterol-kanporaketaren estimulazioa ateroma ereduan, rHDLen administrazio sekuentzialarekin

Abstract

Aterosklerosia arterien gune azpi-endotelialean gertatzen den kolesterol metaketaren ondorioz garatzen da, gaixotasun kardiobaskular larriak eragin ditzakeelarik. Aterosklerosiaren tratamendurako, HDL naturalak (dentsitate handiko lipoproteinak) imitatzen duten hainbat nanopartikulen diseinua burutu izan da (rHDL), ateroma plakako soberazko kolesterola iraizteko helburuarekin. rHDLek kolesterola jasotzeaz gain mikroRNAk edo antagomiRNAk (mikroRNA inhibitzaileak) bezalako molekulak garraiatu ditzakete. Ikerketa honetan, rHDL administrazio sekuentziala ateroma eredu batean ezarri zen. Lehen administrazioan, ABCA1 kolesterol garraiatzailearen adierazpena emendatzeko antagomiRNA bat garraiatu zen rHDL bidez eta bigarrenean, rHDLak soberazko kolesterola jasotzeko gehitu ziren.

Atherosclerosis develops as a result of the accumulation of cholesterol in the subendothelial space of the arteries, which can cause serious cardiovascular diseases. For the treatment of atherosclerosis, the design of several nanoparticles (rHDL) that mimic natural HDLs has been carried out for the purpose of removing excess cholesterol in ateroma plaques. In addition to cholesterol uptake, rHDLs can transport small molecules such as microRNAs, or their inhibitors, antagomiRNAs. In this study, the sequential administration of rHDL was implemented in an atheroma model. In a first administration, an antagomiRNA was transported by rHDLs to increase the expression of ABCA1 cholesterol transporter, and in a second administration, rHDLs were added to remove cholesterol from the cells.