Abstract
BackgroundAtherosclerosis constitutes the leading contributor to morbidity and mortality in cardiovascular and cerebrovascular diseases. Lipid deposition and inflammatory response are the crucial triggers for the development of atherosclerosis. Recently, microRNAs (miRNAs) have drawn more attention due to their prominent function on inflammatory process and lipid accumulation in cardiovascular and cerebrovascular disease. Here, we investigated the involvement of miR-21 in lipopolysaccharide (LPS)-induced lipid accumulation and inflammatory response in macrophages.MethodsAfter stimulation with the indicated times and doses of LPS, miR-21 mRNA levels were analyzed by Quantitative real-time PCR. Following transfection with miR-21 or anti-miR-21 inhibitor, lipid deposition and foam cell formation was detected by high-performance liquid chromatography (HPLC) and Oil-red O staining. Furthermore, the inflammatory cytokines interleukin 6 (IL-6) and interleukin 10 (IL-10) were evaluated by Enzyme-linked immunosorbent assay (ELISA) assay. The underlying molecular mechanism was also investigated.ResultsIn this study, LPS induced miR-21 expression in macrophages in a time- and dose-dependent manner. Further analysis confirmed that overexpression of miR-21 by transfection with miR-21 mimics notably attenuated lipid accumulation and lipid-laden foam cell formation in LPS-stimulated macrophages, which was reversely up-regulated when silencing miR-21 expression via anti-miR-21 inhibitor transfection, indicating a reverse regulator of miR-21 in LPS-induced foam cell formation. Further mechanism assays suggested that miR-21 regulated lipid accumulation by Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) pathway as pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-κB (PDTC) strikingly dampened miR-21 silence-induced lipid deposition. Additionally, overexpression of miR-21 significantly abrogated the inflammatory cytokines secretion of IL-6 and increased IL-10 levels, the corresponding changes were also observed when silencing miR-21 expression, which was impeded by preconditioning with TLR4 antibody or PDTC.ConclusionsTaken together, these results corroborated that miR-21 could negatively regulate LPS-induced lipid accumulation and inflammatory responses in macrophages by the TLR4-NF-κB pathway. Accordingly, our research will provide a prominent insight into how miR-21 reversely abrogates bacterial infection-induced pathological processes of atherosclerosis, indicating a promising therapeutic prospect for the prevention and treatment of atherosclerosis by miR-21 overexpression.
Highlights
Atherosclerosis and its complications rank as the leading cause of death, representing nearly 29% of mortalities globally [1]
We aimed to explore the effects of miR-21 on LPS-induced lipid accumulation and inflammation responses in macrophages
LPS induced miR-21 expression in macrophages LPS is known to be critical for the progress of atherosclerotic plaques [13]
Summary
Atherosclerosis and its complications rank as the leading cause of death, representing nearly 29% of mortalities globally [1]. The large atherosclerotic plaque formation and subsequent rupture is the crucial mechanism underlying the onset of acute ischemic syndromes, including cerebral infarction, stroke, myocardial infarction, and sudden death [2,3,4]. It is commonly accepted that lipidladen foam cell accumulation and inflammation in vessel walls are the hallmarks of the early stage of atherosclerosis, and trigger a series of atherosclerotic complications [5]. It is known that the increasing macrophage foam cell formation induces the production of a large lipid-rich necrotic core, followed by the rupture of vulnerable plaque and subsequent thrombogenesis, a key trigger for acute cardiovascular diseases [6]. Lipid deposition and inflammatory response are the crucial triggers for the development of atherosclerosis. We investigated the involvement of miR-21 in lipopolysaccharide (LPS)-induced lipid accumulation and inflammatory response in macrophages
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
