ABSTRACT
Resumo A aterosclerose é a causa mais comum de doença cardiovascular em todo o mundo, ela está associada a uma alta incidência de eventos clínicos. O acúmulo de evidências elucidou que os RNAs longos não codificantes (LncRNAs) são uma nova classe de transcritos com papéis críticos nos processos fisiopatológicos da aterosclerose. Nesta revisão, resumimos o progresso recente dos LncRNAs no desenvolvimento da aterosclerose. Descrevemos principalmente os diversos mecanismos regulatórios dos LncRNAs nos níveis transcricionais e pós-transcricionais. Este estudo pode fornecer informações úteis sobre os LncRNAs como alvos terapêuticos ou biomarcadores para o tratamento da aterosclerose.
Abstract Atherosclerosis is the most common cause of cardiovascular disease globally, associated with a high incidence of clinical events. Accumulating evidence has elucidated that long non-coding RNAs (lncRNAs) as a novel class of transcripts with critical roles in the pathophysiological processes of atherosclerosis. In this review, we summarize the recent progress of lncRNAs in the development of atherosclerosis. We mainly describe the diverse regulatory mechanisms of lncRNAs at the transcriptional and post-transcriptional levels. This study may provide helpful insights about lncRNAs as therapeutic targets or biomarkers for atherosclerosis treatment.
ABSTRACT
Objective To investigate the role of LPL in enhancing VLDL uptake in mesangial cells and modulating VLDL-mesangial interaction. Methods Human wild type LPL (LPLwt), catalytically inactive LPL (LPL194) or control alkaline phosphatase (AP) were expressed in human mesangiai cell line (HMCL) via adenoviral vectors. The expression of LPL mRNA and protein was detected by RT-PCR and immunoehemistry staining, respectively. LPL activity was assayed by radioisotope labeled liposome substrate. Cellular lipid deposition was visualized by oil red O staining and analyzed quantitatively by standard enzymatic procedures. Effect of LPL on HMCL proliferation was evaluated by colorimetric assay using MTr. MCP-1 mRNA and protein levels in treated HMCLs were determined by real-time quantitative BT-PCB and enzyme-linked immunosorbent assay respectively. For adhesion study, HMCLs were treated with VLDL for six hours, followed by one-hour incubation with Tamm-Horsfall protein-1 (THP-1) cells. Results Compared with HMCLs transfected by Ad-AP, the lever of cellular triglyceride content was sharply increased in Ad-LPLwt Wansfected HMCLs [(109.11±5.01) mg/g protein vs (23.98±3.23) mg/g protein,P<0.01] and was slightly increased in Ad-LPL194 transfected HMCLs [(36.33±2.64) mg/g protein vs (23.98±3.23) mg/g protein, P<0.05]. LPLwt amplified VLDL-driven mesangial cells proliferation. Compared to the HMCL-Ad-AP, MCP-1 mRNA and protein expression increasd by 39% (P<0.05) and 171% (P<0.01) in HMCL-Ad-LPLwt, and the amount of THP-1 cells adhering to HMCL-Ad-LPLwt was increased by 1.69-fold (P<0.05), without significant difference between HMCL-Ad-LPLI94 and HMCL-Ad-AP. Conclusions Overexpression of either active or inactive LPL in HMCLs accelerates VLDL-induced triglyceride accumulation, and enzymolysis action of LPL may be the major factor in this process. Active LPL significantly amplifies VLDL-induced proliferative effect on mesangial cells and enhances monocyte adhesion to mesangial cells through up-regulation of MCP-1. Hence, LPL may be an important contribution to initiation and progression of renal injury mediated by triglyceride-rich lipoproteins.
ABSTRACT
Objective To analyze the dynamic changes in blood lipids and ATP-binding cassette transporter A1 (ABCA1) in peripheral blood monocytes of the patients with type 2 diabetes, and explore the correlations between ABCA1 expression and blood lipids levels and glycometabolism. Methods Human monocytes were isolated from the patients with type 2 diabetes (n=40) and from the healthy individuals (n=40) serve as normal control. ABCA1 was labeled by immune reaction PE fluorescence, then the changes in ABCA1 expression before and after being incubated with the ox-LDL were investigated by flow cytometer. The blood lipid levels, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels in the patients of type 2 diabetes group were determined, and the correlations between ABCA1 and age, blood lipid, and glycometabolic levels were analyzed. Results Plasma levels of triglyceride, non-high density lipoprotein cholesterol (NHDL-C) [low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C)] in the patients of type 2 diabetes group were significantly higher than that in control group (P