Abstract:The level of high density lipoprotein cholesterol (HDL-C) is inversely related with risk of coronary artery disease (CAD) and low level of HDL-C increases the risk of developing cardiovascular diseases. It has been consistent that HDL-C is an independent risk of cardiovascular diseases. However, pharmacological interventions intended to increase HDL-C have not been consistently associated to clinical benefits or anticipated CAD risk reduction. Thus, the function of HDL is more efficient than the HDL-C level to evaluate the risk of cardiovascular events. HDL contains the most abundant proteins than any other lipoprotein. Due to the advances of proteomics, more and more HDL associated proteins have been identified. Besides apolipoproteins and enzymes, the two widely recognized subgroups of HDL proteins, HDL also contains lipid transfer proteins, acute-phase response proteins, complement components, and proteinase inhibitors. Besides lipid metabolism and transport, HDL also plays unexpected roles in immune response, acute phase response, complement activation, metal ion binding and so on. The role of HDL is in a range of diseases, from atherosclerosis to diseases with high risk of cardiovascular events, such as end-stage renal disease, diabetes mellitus. This review summarizes the progression of HDL proteome, function and its roles in CAD as well as diseases with high risk of cardiovascular events.

Abstract:The receptors of apolipoprotein AⅠ and sphingosine 1-phosphate, two main factors mediating the protective effects of high-density lipoprotein (HDL) on blood vessels, are located in adipose tissues. Also, the lipid transfer proteins which mediate HDL remodeling are highly expressed in adipose tissues, suggesting HDL may regulate adipocyte energy metabolism through its components. It is known HDL particles isolated from healthy subjects or recombinant HDLs activate AMP-activated protein kinase (AMPK) in adipocytes and inhibit the oxidation of fatty acids. Further, in vitro and in vivo experiments confirm that the active components in HDL may activate AMPK activity by their receptor pathway, which may contribute to the regulating effects of HDL on adipocyte energy metabolism. It will be expected that studies in the effect of HDL on adipocyte AMPK may provide a new therapeutic target for prevention and treatment of obesity caused by abnormal fat metabolism.

Abstract:Glycine is the simplest amino acid in natural, widely exists in animal body, a key material for one carbon, proteins, peptides, nucleotides, porphyrins and bile salt metabolism. Glycine is not only an inhibitory neurotransmitter in the central nervous system, but also widely involved in the regulation of metabolism, antioxidation and anti-apoptosis intissues. The major objective of this article is to provide an overview of recent findings about the protective effects of glycine on cardiovascular disease caused by myocardial ischemia, hypertension and hyperglycemia.

Abstract:Atherosclerosis is a kind of pathological process characterised by lipid metabolic disorder, which is one of the greatest threats to public health. With the development of genetics and bioinformatics research, non-coding sequences, once considered useless, gradually are getting the attention of the researchers. Long non-coding RNAs (lncRNAs) are involved in biological processes, such as dosage compensation, genetic imprinting and cell cycle control. LncRNAs have effects on growth, metabolism and aging through epigenetic regulation, transcriptional regulation and posttranscriptional. Accumulating studies indicate that lncRNAs are involved in the progresses of injury and repair of endothelial cell, migration and invasion of smooth muscle cell, lipid loading and inflammatory response in macrophages, lipid deposition and the formation of plaques, which affect the progression of atherosclerosis and other cardiovascular diseases.

Abstract:Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for the atherosclerotic cardiovascular disease (ASCVD). Over 70% of circulating LDL-C is metabolized by binding hepatic LDL receptor (LDLR). Therefore, elevation of LDLR expression would reduce the progression of ASVCD. In order to study the molecular mechanism of Curcumin Nieotinate (CurTn) reducing lipid deposition of arterial intima by lowering plasma LDL-C, HepG2 cells were treated with 5, 10, 15 μmol/L CurTn co-incubated with 25 mg/L LDL for 24 h. Cellular lipid was detected by oil red O staining. Cholesterol content was detected by cholesterol quantitative fluorometric kit. LDL uptake was visualized by DiI-LDL and Hoechst33342. The mRNA expression of LDLR and SREBP2 was analyzed by quantitative Real-time PCR (RT-Q-PCR) and protein expression of LDLR, SREBP2 and PCSK9 by Western blotting. Oil Red O staining showed that lipid droplets increased significantly in 10, 15 μmol/L CurTn groups. The content of Cholesterol and DiI-LDL uptake were higher in 10, 15 μmol/L CurTn groups than in control group. RT-Q-PCR and Western blotting showed that CurTn increased LDLR protein expression and decreased PCSK9 protein expression, although CurTn also increased SREBP2 mRNA expression. CurTn had no effect on LDLR mRNA expression in HepG2 cells. These results suggest that PCSK9/LDLR pathway may play a key role in lowering serum LDL-C and attenuating ASCVD risk by CurTn.

Abstract:We previously reported that a human apolipoprotein E mimetic peptide, designated EpK, enhanced the ability of HDL in mediating cholesterol efflux and suppressing LPS-induced proinflammatory cytokine expression in culture macrophage. The aim of this study was to investigate the impact of this peptide on atherosclerosis in apolipoprotein E deficient (apoE^-/-) mice, employed lentivirus expression system to achieve the secretion of EpK in vivo. Eighteen female apoE^-/- mice at 11 months of age were randomly divided into two groups. All mice were injected with pWPI lentivirus (Lv-GFP control group) or pWPI/ EpK lentivirus (Lv-EpK) from retro-orbital venous plexus and fed with a chow diet. Blood samples were collected from mice to determine plasma lipids levels and paraoxonase-1 (PON1) activity during eighteen weeks after lentiviral injection. The extent of atherosclerosis was examined using Oil Red O-stained cross-sections of the aorta root and by en face analysis of the aorta. The mRNA levels of inflammatory cytokines in liver were measured by quantitative real-time PCR and the target protein levels in plasma were detected by Western blot. The results showed that EpK peptide was successfully detected in blood by secreting expression in the liver. There were no obvious differences in plasma lipids levels, lipoprotein profile, apolipoprotein AⅠ level and paraoxonase-1 (PON1) activity between two groups. However, the mean area of atherosclerotic lesions in Lv-EpK mice was significant reduced in aortic arch and total aorta, compared with Lv-GFP control groups (the lesion area of aortic root was (0.87±0.07) mm² vs (1.03±0.08) mm², P < 0.05; the percent area of aortic lesion area was 42% vs 55.8%, P < 0.01). Moreover, expression of EpK resulted in significantly reduced plasma serum amyloid A (SAA) levels and the mRNA levels of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in mouse liver. These results suggest that the apoE mimetic peptide EpK, is able to reduce atherosclerotic plaque in apoE^-/- mice, which the mechanism may be involved in its anti-inflammatory property.

Abstract:To explore the polyunsaturated fatty acids (PUFAs) on the metabolism of apoB100-containing lipoproteins in apolipoprotein E deficient (apoE^-/-) mice, which exists similar symptoms with human typeⅢ familial hyperlipoproteinemia, two months old male apoE^-/- mice were fed the perilla seed oil or safflower oil diet and the control diet, respectively, for 6 weeks. Serum lipids, apoB100 and hepatic HMG-CoA reductase were determined after 6 weeks intervention. The hepatic genes mRNA abundance involved in apoB100 containing lipoprotein metabolism were detected with real time RT-PCR. The hepatic PPARα protein expression was determined by Western blot. The hepatic lipid accumulation was detected by Oil Red O staining after frozen section. The results showed that the mice fed with the perilla seed oil diet decreased the serum LDL-C and apoB100 and HMG-CoA reductase activity. The hepatic genes such as FAS, apoB100, HMG-CoAR, ACAT2, LRP, LDLR and SREBP-1c were decreased significantly compared with the control group. The mRNA and protein expression of PPARα increased significantly in mice fed the perilla seed oil diet, while decreased significantly in mice fed the safflower oil diet compared with the control group. The mice fed the safflower oil diet increased the serum triglyceride and HDL-C and the hepatic apoB100 mRNA level compared with the control group. The hepatic lipid accumulation was decreased in the mice fed the perilla seed oil diet, and was increased in the safflower oil diet compared with the control group. The results indicated that dietary perilla seed oil decreased obviously the metabolism of apoB 100-containing lipoprotein, which was benefit for the atherosclerosis and the fatty liver diseases, providing theoretical basis for the dietary of population and the human typeⅢ familial hyperlipoproteinemia.

Abstract:It has been well known that foam cells formation is one of the hallmarks of early atherosclerosis. Reverse cholesterol transport (RCT) pathway can inhibit the foam cells formation. ATP-binding cassette transporter G1 (ABCG1) plays a crucial role in RCT and anti-atherosclerosis, which mediates the efflux of cholesterol to HDL. Liver X receptor alpha (LXRα) can stimulate cholesterol efflux through ABCG1. It has been well known that adiponectin has cardiovascular protection. In this study, we attempted to clarify the effect of adiponectin on expression of ABCG1, and explored the role of LXRα in the regulation of ABCG1 in RAW 264.7 macrophages. The expression of ABCG1 and LXRα were examined by Real-time quantitative PCR and Western blot analyses. Cellar cholesterol efflux from THP-1 macrophage was analyzed by liquid scintillation counting assays. Our results showed that adiponectin increased ABCG1 expression at both the mRNA and protein levels in a dose-dependent and time-dependent manner. Consequently, adiponectin promoted cholesterol efflux in RAW 264.7 macrophages. Moreover, adiponectin up-regulated the expression of LXRα in a dose-dependent and time-dependent manner in RAW 264.7 macrophages. LXRα small interfering RNA completely abolished the promotion effects of adiponectin. In summary, adiponectin up-regulates ABCG1 expression via the LXRα pathway in RAW 264.7 macrophages.

Abstract:In order to investigate the roles and mechanisms of liver X receptor alpha (LXRα)-ATP binding cassette transporter A1 (ABCA1) pathway in Chlamydia pneumoniae (C. pneumoniae) infection induced macrophage lipid accumulation. THP-1 macrophage derived foam cells were used as the cell model. Cellular cholesterol was determined by high performance liquid chromatography analysis. Cholesterol efflux was determined by liquid scintillator. ABCA1 and LXRα mRNA expression was detected by RT-PCR and protein expression was detected by Western blot. Furthermore, we pretreated the cells with LXRα specific agonist T0901317, and then observed the changes of indexes mentioned above. The result showed that C. pneumoniae infection could increase the content of total cholesterol, free cholesterol and cholesterol ester, inhibit the efflux of cholesterol from cells, and reduce the expression of ABCA1 and LXRα. The suppression of C. pneumoniae infection on ABCA1 expression was significantly attenuated after the use of ABCA1 agonist 8-Br-cAMP or LXR agonist T0901317, correspondingly, cholesterol efflux was promoted and the content of intracellular cholesterol was elevated. These results suggested that the mechanism of C. pneumoniae infection promoting lipid accumulation in macrophages and suppresses cholesterol efflux may be related to LXRα-ABCA1 pathway.

Abstract:Probucol is a potent hypolipidemic drug that decreases plasma high-density lipoprotein cholesterol (HDL-C) levels but attenuates atherosclerosis. However, the detailed mechanisms are not fully understood. The aim of this study was to explore the molecular mechanisms of the HDL-C-lowering and antiatherogenic effects of probucol. New Zealand white rabbits were randomly divided into normal diet group, normal diet+probucol group, high fat diet (HFD) group and HFD+probucol (HFD+P) group. After 7 weeks of treatments, the extent of the atherosclerotic lesions, hepatic lipid accumulation and plasma levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and HDL-C were significantly reduced in HFD+P group as compared to HFD group. Probucol effectively inhibited down-regulation of hepatic scavenger receptor class B typeⅠ (SR-BⅠ) expression, and ATP-binding cassette (ABC) transporters G5 (ABCG5) and G8 (ABCG8) expression in the liver and small intestine induced by HFD but further promoted HFD-induced reduction in hepatic ABC transporter A1 (ABCA1) expression. In addition, probucol also significantly prevented HFD-induced increases of tumor necrosis factor-α, interleukin-1, interleukin-6 and monocyte chemotactic protein-1 levels in the aortic arch and plasma. Thus, our data provide strong evidence that probucol alleviates atherosclerosis through regulating ABCA1, SR-BⅠ, ABCG5 and ABCG8 expression and inhibiting the secretion of proinflammatory cytokines in hypercholesterolemic rabbits.