High-density lipoprotein (HDL) from elderly and reconstituted HDL containing glycated apolipoproteins A-I share proatherosclerotic and prosenescent properties with increased cholesterol influx.

High-density lipoprotein (HDL) is a strong antioxidant, anti-inflammatory, and antisenescence molecule. However, in the current study, HDL from the elderly group (E-HDL) exhibited increased glycation with apolipoprotein (apo) A-I multimerization and decreased phospholipid content. Similarly, glycated apoA-I (gA-I) by fructosylation has a covalently multimerized band without a crosslinker and impaired phospholipid-binding ability. Treatment of human dermal fibroblasts and macrophages with E-HDL and gA-I caused more severe cellular senescence and foam cell formation, respectively; however, treatment with HDL from a young group (Y-HDL) and native apoA-I (nA-I) suppressed senescence and atherosclerosis. E-HDL(3) and reconstituted HDL (rHDL) containing gA-I showed enhanced cholesterol influx into macrophages compared with Y-HDL(3) and nA-I-rHDL. In conclusion, E-HDL and gA-I-rHDL share similar physiologic properties in macrophages and human dermal fibroblasts. E-HDL and gA-I-rHDL exacerbated cellular senescence and atherosclerosis with increased cellular cholesterol influx.