Effects of Atorvastatin on Oxidized Low-Density Lipoprotein-induced Proliferation, Apoptosis, and Matrix Metalloproteinase-9 Expression in Human Macrophages

Abstract

Atorvastatin (ATV), an HMG-CoA reductase inhibitor, is utilized in the treatment of atherosclerotic diseases. Mononuclear Macrophages (MMs) are critical immune cells involved in atherosclerosis progression, participating in processes such as foam cell formation, cytokine secretion, and the development of fibrous cap and lipid core. To further elucidate the mechanism by which ATV exerts its therapeutic effects on atherosclerosis through the modulation of healthy human MM biological processes, this work investigated the impact of ATV on the expression of matrix metalloproteinases-9 (MMP-9) in healthy human MMs induced by oxidized low-density lipoprotein (ox-LDL), along with mechanisms involved Mononuclear cells from healthy individuals were isolated using density gradient centrifugation and differentiated into macrophages, which were subsequently divided into three groups: Blank, ox-LDL, and ATV (0.01, 0.1, and 1.0 μmol/L). Cell proliferation was assessed using MTT assay, while apoptosis was evaluated by flow cytometry. The expression levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and MMP-9 mRNA were measured using quantitative real-time PCR, and MMP-9 protein EL was analyzed via Western blotting. Relative to the Blank group, ox-LDL group exhibited increased cell proliferation activity and reduced apoptosis rates, along with elevated mRNA expression levels of inflammatory genes IL-6, IL-1β, and TNF-α. Additionally, both MMP-9 mRNA and protein expression levels were greatly higher (P<0.05). In contrast, the different concentrations of ATV groups showed decreased cell proliferation activity, increased apoptosis rates, and reduced mRNA expression levels expression levels of inflammatory genes IL-6, IL-1β, and TNF-α, and decreased MMP-9 mRNA and protein expression levels versus ox-LDL group (P<0.05). Notably, as the concentration of ATV increased, the alterations in cell proliferation, apoptosis, inflammatory gene expression, and MMP-9 levels became more pronounced (P<0.05). In summary, ATV can downregulate MMP-9 expression and inhibit inflammatory gene expression, thereby influencing the proliferation and apoptosis processes of human MMs.