Macrophage Differentiation Selectively Downregulates RPS15A While Preserving RPL13A and RPL17 Expression in...

Atherosclerosis is a chronic inflammatory condition that is considered a major contributor to cardiovascular disease (CVD). Atherosclerosis is linked to multiple risk factors, including dyslipidemia, particularly elevated levels of low-density lipoprotein (LDL), which can infiltrate the arterial intima and contribute to disease initiation. Modification of LDL into its oxidized form by myeloperoxidase has been proposed as a physiologically relevant model for LDL oxidation that reflects what happens during the initiation and progression of atherosclerosis. Interestingly, the latter form of oxidized LDL has been shown to induce a myriad of inflammatory reactions within a variety of cells that are involved in atherogenesis. In macrophages (Mφ), accumulation of modified LDL leads to the formation of foam cells which constitute the hallmark of atherosclerosis. Remarkably, Mφs exhibit considerable plasticity and can adopt different phenotypes in response to microenvironmental stimuli. Classically activated M1 macrophages are generally associated with pro-inflammatory responses, whereas alternatively activated M2 macrophages are associated with anti-inflammatory and tissue-repair functions. On the other hand, ribosomal proteins (RPs) have been associated with a range of extra-ribosomal functions that extend beyond their well-recognized role in translation. Notably, multiple RPs, including RPS3, RPL13A, RPS15A and RPL17, have been involved in CVD, playing contrasting roles in the pathogenesis of the disease. In our present study, we investigated, for the first time, the effect of Mφ differentiation, polarization, and Mox-LDL treatment on the expression levels of ribosomal proteins RPS3, RPL13A, RPS15A and RPL17 by using the THP-1 cell model in an effort to reveal potential roles of these ribosomal proteins in Mφ pathobiology. Our study showed that differentiation and polarization significantly downregulate RPS15A expression in THP-1 M0-, M1- and M2-Mφs, whereas differentiation leads to a non-significant trend toward reduced RPS3 expression in M1-Mφs compared with monocytes (p = 0.059), while no significant changes in RPL13A and RPL17 expression have been reported under our experimental conditions. These findings indicate that THP-1 monocyte differentiation and macrophage polarization are associated with selective downregulation of RPS15A, whereas the expression of the other investigated ribosomal proteins is largely preserved. Further studies, particularly in primary human macrophages and using functional approaches, are warranted to validate these findings and determine their biological significance and potential relevance to atherosclerosis.