TY - JOUR
T1 - Reduced Uptake of Oxidized Low-Density Lipoprotein by Macrophages Using Multiple Aptamer Combinations
AU - Khongwichit, Soemwit
AU - Swangphon, Piyawut
AU - Nualla-Ong, Aekkaraj
AU - Prompat, Napat
AU - Amatatongchai, Maliwan
AU - Lieberzeit, Peter A.
AU - Chunta, Suticha
N1 - Publisher Copyright:
© 2025 The Authors. Published by American Chemical Society.
Accession Number
WOS:001391402800001
PY - 2025
Y1 - 2025
N2 - The accumulation of oxidized low-density lipoprotein (oxLDL) in macrophages leads to the formation of foam cells and atherosclerosis development. Reducing the uptake of oxLDL in macrophages decreases the incidence and progression of atherosclerosis. Four distinct single-strand DNA sequences, namely, AP07, AP11, AP25, and AP29, were selected that demonstrated specific binding to distinct regions of oxidized apolipoprotein B100 (apoB100; the protein component of oxLDL) with low HDOCK scores. These four DNA sequences were combined to generate aptamers that selectively bound to labeled Dil-oxLDL, and were subsequently added to murine RAW 264.7 macrophages to test their inhibitory effects using fluorescence spectrometry. The four combined aptamers at 10 μM reduced oxLDL uptake by 79 ± 4% compared to that of the untreated aptamer group. Flow cytometry data demonstrated that macrophages treated with aptamers reached only 32.6% of the Dil-oxLDL signal, a 50% reduction in fluorescence emission relative to that of the untreated group (64.4% Dil-oxLDL signal). Binding the four combined aptamers to the oxLDL surface disrupted the interaction between oxLDL and CD36 via cyclic voltammetry, effectively decreasing the level of uptake of oxLDL by macrophages. Results suggested that these aptamers could be used as alternative compounds to prevent the formation of foam cells, hence providing antiatherosclerosis activity.
AB - The accumulation of oxidized low-density lipoprotein (oxLDL) in macrophages leads to the formation of foam cells and atherosclerosis development. Reducing the uptake of oxLDL in macrophages decreases the incidence and progression of atherosclerosis. Four distinct single-strand DNA sequences, namely, AP07, AP11, AP25, and AP29, were selected that demonstrated specific binding to distinct regions of oxidized apolipoprotein B100 (apoB100; the protein component of oxLDL) with low HDOCK scores. These four DNA sequences were combined to generate aptamers that selectively bound to labeled Dil-oxLDL, and were subsequently added to murine RAW 264.7 macrophages to test their inhibitory effects using fluorescence spectrometry. The four combined aptamers at 10 μM reduced oxLDL uptake by 79 ± 4% compared to that of the untreated aptamer group. Flow cytometry data demonstrated that macrophages treated with aptamers reached only 32.6% of the Dil-oxLDL signal, a 50% reduction in fluorescence emission relative to that of the untreated group (64.4% Dil-oxLDL signal). Binding the four combined aptamers to the oxLDL surface disrupted the interaction between oxLDL and CD36 via cyclic voltammetry, effectively decreasing the level of uptake of oxLDL by macrophages. Results suggested that these aptamers could be used as alternative compounds to prevent the formation of foam cells, hence providing antiatherosclerosis activity.
KW - Combined aptamers
KW - foam cell formation
KW - macrophages
KW - oxidized low-density lipoprotein (oxLDL)
KW - therapeutic agent
UR - http://www.scopus.com/inward/record.url?scp=85214289120&partnerID=8YFLogxK
U2 - 10.1021/acsabm.4c01432
DO - 10.1021/acsabm.4c01432
M3 - Article
AN - SCOPUS:85214289120
SN - 2576-6422
JO - ACS applied bio materials
JF - ACS applied bio materials
ER -