Legumain: a potential biomarker for atherosclerosis.

Atherosclerosis is a lipid-driven chronic inflammatory disease that poses a serious threat to health. Legumain (LGMN), also known as asparagine endonuclease, is a new type of cysteine proteases that can specifically hydrolyze substrate molecules containing asparagine residues. It has anti-apoptotic effects in mammals and plays an antigen-presenting role in inflammatory response. Several studies have found that LGMN can activate multiple signal pathways to promote cell apoptosis and migration, inflammatory response, and the development of atherosclerosis. Importantly, LGMN exerts pro-atherogenic effects by participating in a variety of pathophysiological mechanisms of atherosclerosis, including vascular remodeling, inflammatory response, plaque stability, and the degradation of extracellular matrix. In the present review, we describe the LGMN distribution, structure, generation, and functional partners. Furthermore, we summarize the relationship between LGMN and atherosclerosis. Based on the relationship between LGMN and atherosclerosis, LGMN may be a potential biomarker for atherosclerosis.

TIGAR mitigates atherosclerosis by promoting cholesterol efflux from macrophages.

BACKGROUND AND AIMS: TP53-induced glycolysis and apoptosis regulator (TIGAR) is now characterized as a fructose-2,6-bisphosphatase to reduce glycolysis and protect against oxidative stress. Recent studies have demonstrated that TIGAR is associated with cardiovascular disease. However, little is known about its role in atherosclerogenesis. In this study, we aimed to investigate the effect of TIGAR on atherosclerosis and explore the underlying molecular mechanism. METHODS: The Gene Expression Omnibus (GEO) datasets were used to analyze the differential expression of relative proteins. THP-1-derived macrophages were used as an in vitro model and apolipoprotein E-deficient (Apoe-/-) mice were used as an in vivo model. [3H] labeled cholesterol was used to assess the capacity of cholesterol efflux and reverse cholesterol transport (RCT). Both qPCR and Western blot were used to evaluate the mRNA and protein expression, respectively. Lentiviral vectors were used to disturb the expression of TIGAR in vitro and in vivo. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaques in Apoe-/- mice fed a Western diet. Conventional assay kits were used to measure the levels of reactive oxygen species (ROS), plasma lipid profiles and 27-hydroxycholesterol (27-HC). RESULTS: Our results showed that TIGAR is increased upon the formation of macrophage foam cells and atherosclerosis. TIGAR knockdown markedly promoted lipid accumulation in macrophages. Silencing of TIGAR impaired cholesterol efflux and down-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) and ABCG1 by interfering with liver X receptor α (LXRα) expression and activity, but did not influence cholesterol uptake by macrophages. Additionally, this inhibitory effect of TIGAR deficiency on cholesterol metabolism was mediated through the ROS/CYP27A1 pathway. In vivo experiments revealed that TIGAR deficiency decreased the levels of ABCA1 and ABCG1 in plaques and aorta and impaired the capacity of RCT, thereby leading to the progression of atherosclerosis in Apoe-/- mice. CONCLUSIONS: TIGAR mitigates the development of atherosclerosis by up-regulating ABCA1 and ABCG1 expression via the ROS/CYP27A1/LXRα pathway.

Long non-coding RNA PCA3 inhibits lipid accumulation and atherosclerosis through the miR-140-5p/RFX7/ABCA1 axis.

OBJECTIVE: The purpose of this study was to explore the role of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in atherosclerosis and the underlying mechanism. METHODS: The Gene Expression Omnibus (GEO) datasets were used to divide differentially expressed lncRNAs, microRNAs (miRNAs), and mRNAs. The expression of PCA3, miR-140-5p, RFX7 and ABCA1 were determined by qPCR or Western blot in ox-LDL-treated macrophages. Macrophage lipid accumulation s was evaluated using the Oil Red O staining and high-performance liquid chromatography. Target relationships among PCA3, miR-140-5p, RFX7, and ABCA1 promoter area were validated via dual-luciferase reporter gene assay or chromatin immunoprecipitation assay. The apoE-/- mouse model in vivo was designed to evaluate the effect of PCA3 on the reverse cholesterol transport (RCT) and atherosclerosis. RESULTS: PCA3 was down-regulated in foam cells, whereas miR-140-5p was highly expressed. Overexpression of PCA3 promoted ABCA1-mediated cholesterol efflux and reduced lipid accumulation in macrophages. Besides, RFX7 bound to the ABCA1 promoter and increased ABCA1 expression. Targeted relationships and interactions on the expression between miR-140-5p and PCA3 or RFX7 were elucidated. PCA3 up-regulated ABCA1 expression by binding to miR-140-5p to up-regulate RFX7 and ABCA1 expression in macrophages. PCA3 promoted RCT and impeded the progression of atherosclerosis by sponging miR-140-5p in apoE-/- mice. Meanwhile, miR-140-5p also inhibit ABCA1 expression via downregulation of RFX7 to impede RCT and aggravate atherosclerosis. CONCLUSIONS: lncRNA PCA3 promotes ABCA1-mediated cholesterol efflux to inhibit atherosclerosis through sponging miR-140-5p and up-regulating RFX7.

[Distribution characteristics of soil cadmium in different textured paddy soil profiles and its relevance with cadmium uptake by crops].

Adopting atomic absorption spectrometry (novAA400), the present study investigated the distribution characteristics of soil cadmium (Cd) in different textured paddy soil profiles under rice-wheat rotation and its correlation with Cd uptake by rice and wheat in Chengdu Plain through repeatedly taking soil and plant samples at the fixed sites in the field. The results revealed that Cd in the paddy soil profiles was mainly concentrated at the plough layer (0-15 cm) that obviously featured 'Cd accumulates towards the rooting layer'. Soil total Cd and available Cd (1 mol x L(-1) MgCl2 extraction) in the profile declined with soil depths and its average values at 30-45 cm only accounted for 47.60% and 39.49% of those at 0-15 cm. The potential downward movement of Cd in the different textured soil profiles was observed as sandy loam > heavy loam > loam. There was no significant correlation between soil pH and available Cd(r = - 0.46) at 0-15 cm soil depth, while significantly negative correlations between soil pH and available Cd were observed at 15-30 cm (r = -0.78) and 30-45 cm (r = -0.86). The results further demonstrated that the Cd contents in either grain or straw of rice and wheat were not well correlated with soil total Cd at any soil depth (r = -0.092-0.383 for rice and r = 0.174-0.424 for wheat), but significantly correlated with soil available Cd at 0-15 cm and at 15-30 cm (r = 0.766*-0.953**) despite insignificant correlation at 30-45 cm (r = 0.526-0.584). It is strongly suggested that the soil available Cd can be used as a better criterion than the total soil Cd to rate Cd contaminated soils in relation to safety of agricultural products.