CXCL16 may be a predisposing factor to atherosclerosis: An animal study.

Atherosclerosis (AS) is a chronic inflammatory process initiated when lipoprotein is retained in the arterial wall. Leukocyte recruitment accelerates this process. CXC chemokine ligand 16 (CXCL16) acts as a chemokine to attract immune cells and also facilitates the phagocytosis process of modified low­density lipoprotein. Whether CXCL16 promotes or inhibits the pathological process of AS remains to be elucidated. To clarify this, CXCL16 gene was introduced into C57BL/6J wild­type mice to establish a stable CXCL16 overexpression mouse model. The initial changes of AS in mice were induced by high­fat diet (HFD). To study how the interaction of HFD and CXCL16 affected fatty acid metabolism and deposition, body weight and plasma lipid profile were assessed. Soluble CXCL16, matrix metalloproteinase­9, monocyte chemoattractant protein­1 and intercellular adhesion molecule­1 were detected by immunohistochemistry and ELISA to identify how CXCL16 affects AS lesion formation. The present study suggested that overexpression of CXCL16 combined with HFD lead to atherogenesis by upregulating the aforementioned inflammatory related genes at a protein level. The present study was the first, to the best of the authors' knowledge, to build a CXCL16 homozygous transgenic mice model to study how overexpressed CXCL16 is associated with AS for intervening in the occurrence and development of AS.

H2S inhibits atrial fibrillation-induced atrial fibrosis through miR-133a/CTGF axis.

AIM: Atrial fibrillation (AF) is a common clinical arrhythmia and can cause a variety of complications. To study the therapeutic effect of H2S in atrial fibrosis and explore the important role of miR-133a, in vitro experiments in human atrial fibroblasts (HAFs) were conducted. METHODS: The fibrosis in HAFs was induced by Ang II. The expression levels of miR-133a and CTGF in HAFs were examined by qRT-PCR. The proliferation and migration of HAFs were detected by CCK-8 and cell scratch assays. The protein expressions of CTGF, collagen I, collagen III and α-SMA were detected by western blotting. The dual-luciferase reporter gene was used to detect the interaction between miR-133a and CTGF. RESULTS: The proliferation and migration of HAFs stimulated by Ang II were enhanced, the expression of miR-133a was reduced, and the levels of CTGF and fibrosis markers (collagen I, collagen III and α-SMA) were increased. Furthermore, H2S reduced fibrosis, proliferation and migration of HAFs induced by Ang II. Accordingly, overexpression of miR-133a inhibited the proliferation and migration ability on Ang II-induced HAFs, and decreased the protein expressions of related fibrosis markers and CTGF. Meanwhile, miR-133a inhibitor could reverse the inhibition effect of H2S on proliferation and migration in HAFs by Ang II-induced. By targeting CTGF, miR-133a inhibited the expression of CTGF. CONCLUSION: H2S improved myocardial cell fibrosis by significantly increasing the expression of miR-133a, and CTGF might be a potential target for miR-133a to play an important role in myocardial fibrosis.

Oxidized low-density lipoprotein accelerates the injury of endothelial cells via circ-USP36/miR-98-5p/VCAM1 axis.

Circular RNAs (circRNAs) are a group of RNAs featured by a covalently closed continuous loop structure. This study aimed to uncover the function and mechanism of circ-ubiquitin specific peptidase 36 (USP36) in endothelial cells treated with oxidized low-density lipoprotein (ox-LDL). The levels of circ-USP36, microRNA-98-5p (miR-98-5p) and vascular cell adhesion molecule 1 (VCAM1) were examined by a quantitative real-time polymerase chain reaction (qRT-PCR). The viability, apoptosis and inflammation were detected by (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Western blot assay was performed to detect the expression of apoptosis and proliferation-related markers and VCAM1 protein level. The targets of circ-USP36 and miR-98-5p were searched using starBase website, and dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the above predictions. Ox-LDL exposure induced the upregulation of circ-USP36 in HUVEC cells. Circ-USP36 accelerated ox-LDL-induced apoptosis, inflammatory and viability inhibition of HUVEC cells. MiR-98-5p was a direct downstream gene of circ-USP36. Circ-USP36 promoted the injury of ox-LDL-induced HUVEC cells through targeting miR-98-5p. VCAM1 could bind to miR-98-5p, and the protective effects of miR-98-5p accumulation on ox-LDL-induced HUVEC cells were reversed by the transfection of VCAM1. VCAM1 was regulated by circ-USP36/miR-98-5p signaling in HUVEC cells. Ox-LDL promoted the apoptosis and inflammation but suppressed the viability of HUVEC cells through upregulating circ-USP36, thus elevating the expression of VCAM1 via miR-98-5p.