Abstract

Atherosclerosis is characterized by the buildup of lipid deposits and plaque formation resulting from consistently elevated levels of LDL-cholesterol (LDL-C) in the blood. This study investigates the effects of aaptamine on the regulation of statin action concerning PCSK9 and LDL receptor (LDLR) expression, as well as LDL-C uptake in human liver cells. This research sought to assess the impact of aaptamine on the statin-induced elevation of PCSK9 expression, LDLR levels, and LDL-C uptake. The MTS assay was utilized to evaluate cytotoxicity. PCSK9 mRNA levels were quantified using real-time PCR, and protein expression was assessed through western blotting. Immunohistochemistry was utilized to evaluate LDLR levels and LDL-C uptake in hepatic cells. Results indicate that simvastatin elevated PCSK9 gene expression, achieving a maximum increase of fourfold. Co-incubation of aptamine in simvastatin-treated cells significantly reduced PCSK9 gene expression. The co-treatment of cells with simvastatin and aaptamine resulted in a threefold increase in LDLR protein levels and LDL-C uptake rates. The results indicated that aptamine reduced the effects of simvastatin on PCSK9 and LDLR expression, thereby enhancing LDL-C uptake by liver cells. This suggests that aaptamine may be a viable candidate for further development in the context of cardiovascular disease.

Key words: Atherosclerosis, PCSK9, Statin, Aaptamine, LDL-C, Marine Natural Compound.