Abstract:Aim To investigate the effect of CDR132L (miR-132 antisense oligonucleotide) on vascular remodeling and function in mice with hypertension and hyperlipidemia, and explore its possible mechanism. Methods A total of 30 8-week-old male C57BL/6 mice were randomly divided into three groups:control group, model group and CDR132L group, with 10 mice in each group. The control group received with a standard diet while the model group and CDR132L group received N-nitro-L-arginine methyl ester (L-NAME) and high-fat diet to induce hypertension and hyperlipidemia. The CDR132L group was administered with intraperitoneal injection of CDR132L at a dose of 20 mg/kg once weekly for six consecutive weeks, whereas the control group and the model group were given intraperitoneal injection of an equivalent volume of normal saline. The tail-cuff method was utilized for blood pressure measurement, blood lipid and glucose levels were assayed by an automatic biochemical analyzer, the thoracic aorta structure was observed by HE staining, endothelium-dependent relaxation of the thoracic aorta was evaluated by the vascular ring test, the expression level of miR-132 in the thoracic aorta was measured by qPCR, the protein expression levels of Gab1 and endothelial nitric oxide synthase (eNOS) in the thoracic aorta were determined by Western blot. Results Compared with the control group, the model group demonstrated notable rises in systolic and diastolic blood pressure, serum triglyceride, total cholesterol levels, and body weight. Moreover, the intima of thoracic aorta and the thickness of vascular wall was uneven, the smooth muscle cells of the tunica media were arranged irregularly, with a large amount of fat deposition in the vascular wall, and the endothelium-dependent relaxation response of thoracic aorta was decreased (P＜0.05). The expression level of miR-132 in the thoracic aorta was significantly increased (P＜0.05), while the expression level of Gab1 and eNOS protein was markedly decreased (P＜0.05). Compared with the model group, the CDR132L group showed no significant differences in systolic and diastolic blood pressure, serum triglyceride and total cholesterol levels, as well as body weight (P＞0.05).However, the CDR132L group exhibited a complete and smooth intima of the thoracic aorta with minimal intravascular lipid deposition, the thickness of the vascular wall was uniform, the smooth muscle cells of the tunica media were arranged orderly, accompanied by enhanced endothelium-dependent relaxation response of the thoracic aorta (P＜0.05). The expression level of miR-132 in the thoracic aorta was significantly decreased (P＜0.05), while the expression levels of Gab1 and eNOS protein were significantly increased (P＜0.05). Conclusion CDR132L can improve vascular remodeling and endothelium-dependent relaxation in hypertensive and hyperlipidemia mice, which may be related to the decrease of miR-132 expression level and the up-regulation of Gab1 and eNOS protein expression levels in the thoracic aorta.

Abstract:Aim To observe the effect of intraperitoneal injection of hydrogen-rich saline (HRS) on reverse cholesterol transport in golden hamsters with high fat diet. Methods The male golden hamsters were divided into three groups:chow diet group, high-fat diet group, and high-fat diet＋HRS group. After 12 weeks of high-fat diet feeding and HRS administration, macrophages labeled with 3H-cholesterol were injected into hypercholesterolemic golden hamsters, and then radioactivity in blood, liver, bile, and feces was measured. RT-qPCR and Western blot were used to assess the transcription and protein expression levels of cholesterol reverse transport-related genes in liver tissue. Results Long-term feeding with a high-fat diet induced significant hyperlipidemia and liver lipid accumulation in golden hamsters. Compared with the high-fat diet group, after HRS intervention, the body mass of golden hamsters decreased (P＜0.01), plasma TC and LDLC significantly decreased (P＜0.05), TG slightly decreased (P＝0.11), HDLC significantly increased (P＜0.01), oxidative stress index MDA in plasma and liver significantly decreased (P＜0.05 or P＜0.01), antioxidant index glutathione (GSH) significantly increased (P＜0.01), liver weight/body weight ratio slightly decreased (P＝0.05), TC and TG in liver decreased by 10.8% (P＝0.05) and 20.1% (P＜0.01), respectively. Liver steatosis was significantly relieved, but there was no significant change in inflammatory factor levels. In isotopic tracing, high-fat diet fed golden hamsters treated with HRS showed decreased 3H radioactivity in plasma at 24 and 48 hours by 16.5% (P＜0.01) and 8.9% (P＜0.05) respectively, while increased 3H radioactivity was observed in liver, bile, and feces by 1.2-fold (P＜0.05), 1.2-fold (P＝0.08), and 1.1-fold (P＝0.08) respectively, compared to those fed a high-fat diet alone. Furthermore, RT-qPCR and Western blot analyses of liver tissue demonstrated that HRS intervention resulted in a decrease of CD36, scavenger receptor-B1 (SR-B1), and low density lipoprotein receptor (LDLR) protein levels by 39.5% (P＜0.05), 40.5% (P＜0.01), and 28.0% (P＜0.01) respectively, an increase of ATP-binding cassette transporter G5 (ABCG5) and sterol regulatory element-binding protein (SREBP2) protein levels by 1.5-fold (P＜0.05) and 1.3-fold (P＜0.01), and an increase of mRNA levels of ATP-binding cassette transporter A1 and G8 by 2.9-fold (P＜0.05) and 3.2-fold (P＜0.01) respectively in high-fat diet-fed hamsters. Conclusions Intraperitoneal injection of HRS promotes reverse cholesterol transport in high-fat diet-fed golden hamsters and exerts lipid-lowering effects. Additionally, intraperitoneal injection of HRS may alleviate hepatic lipid accumulation by inhibiting hepatic lipid uptake and promoting cholesterol excretion from liver.

Abstract:Aim To investigate the effects of long-term ezetimibe on hyperlipidemia and genes involved in lipid metabolism in the liver of the LDLR＋/－ hamster. Methods Male LDLR＋/－ hamsters were randomly divided into two groups:the vehicle group and the ezetimibe group (25 mg/(kg·d)). Animals were free to access water and high-fat diet. After 20-week administration, hamsters were sampled after overnight fasting. The plasma levels of total cholesterol (TC), triglyceride (TG), total bile acid (TBA), non-esterified fatty acid (NEFA) and aspartate aminotransferase (AST) were detected by assay kits. Mixed plasma in each group was further separated via an KTA fast protein liquid chromatography (FPLC) system and the TC and TG levels in each fraction were also detected. The expression of multiple genes in the liver and proteins in the plasma was determined by qRT-PCR and Western blot, respectively. Results Long-term ezetimibe intervention significantly decreased plasma TC, TG, TBA, NEFA and AST levels, and apolipoprotein B protein expression in the LDLR＋/－hamsters, and had no effect on the protein levels of lipoprotein lipase (LPL) and proprotein convertase subtilisin/kexin-type 9 (PCSK9) and the activity of LPL. Further KTA-FPLC analysis demonstrated that ezetimibe reduced the TC and TG levels in all the lipoprotein fractions. In the liver, ezetimibe significantly reduced TC, but not TG concentration. Furthermore, ezetimibe significantly increased the mRNA expression of sterol regulatory element binding protein 2 and PCSK9 and dramatically decreased the expression of liver X receptor α, cholesterol 7α-hydroxylase A1, ATP-binding cassette transporter G5 (ABCG5) and ABCG8 in the liver. Conclusion Long-term ezetimibe intervention reduces hyperlipidemia and displays complex modulatory effects on the genes involved in lipid homeostasis in LDLR＋/－ hamsters.

Abstract:Hyperlipidemia is an important risk factor for chronic cardiovascular and cerebrovascular diseases such as coronary heart disease and cerebral infarction, and the prevention and treatment of dyslipidemia has become one of the important methods for the prevention of coronary heart disease. At present, most of the indicators used to evaluate the efficacy of hyperlipidemia are total cholesterol, triglycerides, low density lipoprotein, high density lipoprotein and body weight. Atherosclerosis index, leptin, adiponectin, and total fecal bile acid are four new indicators used to evaluate the efficacy of hyperlipidemia. This paper reviews the four indicators for the evaluation in the treatment of hyperlipidemia.

Abstract:Aim To investigate the effects of Xuezhikang (XZK) on low-density lipoprotein (LDL) subfractions and oxidized low-density lipoprotein (ox-LDL) in patients with hyperlipidemia. Methods A total of 40 subjects (20 patients with hyperlipidemia and 20 healthy subjects) who were not treated with lipid-lowering drugs were selected consecutively and divided into the XZK group (n=20) and the control group (n=20). The plasma LDL subfractions, ox-LDL were examined by using the Lipoprint system at baseline and again after 8 weeks. Results Data showed that XZK could significantly decrease not only plasma LDLC levels, total cholesterol, triglycerides, and apolipoprotein B (P＜0.05), but also ox-LDL (P＜0.05). At the same time, XZK reduced the concentration of small LDLC (P＜0.05) and the percentage of the small LDL subfraction (P＜0.05). Conclusion XZK treatment for 8 weeks significantly improved the blood lipid profile, reduced the concentration and percentage of atherogenic small LDLC, and reduced the level of oxidative stress.

Abstract:Aim To explore the current situation, hotspots and trends of blood lipid research in Chinese population from 2009 to 2019. Methods From 2009 to 2019, literatures related to blood lipid research were retrieved on China National Knowledge Infrastructure (CNKI). Bibliographic item co-occurrence matrix builder (BICOMB) and graphical clustering toolkit (gCLUTO) were used for word frequency analysis and clustering analysis. Results A total of 3 022 literatures were searched, with 47 high-frequency words and with frequency greater than or equal to 31. The results of cluster analysis showed that from 2009 to 2019, the research hotspots of blood lipid in China mainly focused on five aspects:the epidemiology of hyperlipidemia in Chinese population, the chronic diseases related to lipids or atherosclerosis, the theory of oxidized low density lipoprotein cholesterol fat, lipid regulating drugs, and Chinese characteristic lipid regulating therapy. Conclusion Many scholars are committed to the study of disease mechanism, lipid-lowering treatment strategy and new drug research and development, but the study of non-drug intervention in lipid management is very rare, so it is urgent to carry out health education in nursing and promote intervention, so as to improve the awareness rate, treatment rate and standard-reaching rate of lipid management.

Abstract:Coronary artery endothelial injury is the initiating and the most critical factor of atherogenesis. For a long time, researchers have focused on the mechanism of endothelial injury induced by oxidized low density lipoprotein(ox-LDL). With the development of new technologies and methods, the role of micro-RNA (miRNA) in the process of endothelial cell injury induced by ox-LDL has been gradually discovered. This review briefly describes the miRNAs involved in endothelial injury such as endothelial inflammation, autophagy, apoptosis and dysfunction under the condition of hyperlipidemia. Summarizing these miRNAs may permit new ideas for the prediction, diagnosis and even treatment of coronary atherosclerosis.

Abstract:Aim To investigate the effect of Songling Xuemaikang (SX) on vascular endothelial function and its protective mechanism in rats with cerebral atherosclerosis (CAS). Methods SD rats were divided into 3 groups:control group, CAS group and the SX group. CAS model of hypertension and hyperlipidemia was established in the CAS group and the SX group. Rats in the SX group were treated by Songling Xuemaikang. The blood pressure and blood lipid indexes of each group of rats were detected and compared. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of basilar artery and brain tissue. Serum levels of nitric oxide (NO) and endothelin-1 (ET-1) were measured by enzyme-linked immunosorbent assay. The expression levels of Notch1 and Hes1 protein were detected by Western blot. Results The blood pressure and blood lipid levels of the CAS group were significantly higher than those of the control group (P＜0.05). The blood pressure and blood lipid levels of the SX group were significantly lower than those of the CAS group (P＜0.05). The basilar artery morphology of the control group was normal. In the CAS group, the intima of the rat was damaged, the lipid was deposited in the intima of the artery, and the smooth muscle cells in the middle layer of the artery were disordered. The pathological morphology of the SX group was between the control group and the CAS group. The NO of the CAS group was significantly lower than that of the control group and the ET-1 was significantly higher than the control group (P＜0.05). The NO of the SX group was significantly higher than that of the CAS group and the ET-1 was significantly lower than the CAS group (P＜0.05). In the control group, the brain tissue structure was completed, the cells were normal, the nucleolus was obvious, and the cytoplasm was abundant. In the CAS group, the brain cells of the rats were arranged one time, the nucleoli were not obvious, and the cytoplasm showed empty halos. The morphology and arrangement of the SX group were basically normal, and the nucleolus and cytoplasm were clear. The levels of Notch1 and Hes1 in the CAS group were significantly higher than those in the control group (P＜0.05). The levels of Notch1 and Hes1 in the SX group were significantly lower than those in the CAS group (P＜0.05).Conclusion Songling Xuemaikang has the effect of protecting vascular endothelial cells caused by hypertension and hyperlipidemia and antagonizing brain damage, which may be related to the inhibition of Notch pathway.

Abstract:Monocytes are important mediators of the innate immunity and play crucial roles in various inflammatory diseases, including vascular inflammation and atherosclerosis (As). Hyperlipidemia can accelerate cardiovascular disease progression, especially As. Under hyperlipidemia, circulating monocytes can take up lipids, become foamy monocytes and change phenotypes, which may contribute to development of As. For a long time, the response of monocytes and their different subtypes to hyperlipidemia and the effect on As have been the focus of research. This paper discusses the characteristics of monocyte subtypes in human and mice, the effects of hyperlipidemia on monocytes, and the effects of monocytes on As, and focuses on the research progress of monocytes affecting As process through lipid phagocytosis, foam cell formation, patrolling and migration into plaques.

Abstract:Aim To investigate the effects and mechanisms of quantum lipid-lowering instrument on lipid regulation. Methods High fat diet and 10% fructose were used to establish a rat model of hyperlipidemia. The output power of the quantum lipid-lowering instrument was 70 μW/cm2, and the treatment time was 5~10 minutes for each time,1~2 times a day. Elisa kit was used to detect serum lipid levels and Western blot was used to measure the expressions of key protein in lipid metabolic and inflammatory pathways. Results Quantum lipid-lowering instrument can improve the disorder of blood lipid metabolism, regulate blood lipid balance, reduce inflammation, alleviate liver function damage, alleviate oxidative damage, increase the activity of lipid metabolism-related enzymes, and inhibit the activity of fatty acid synthase which is caused by hyperlipidemia. Western blot showed that Quantum lipid-lowering instrument could alleviate inflammation by regulating the expression levels of nuclear factor κB (NF-κB), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6);modulate the expression of peroxisome proliferators-activated receptors α (PPARα) which could improve lipid metabolism;regulate the sterol-regulatory element binding proteins 2 (SREBP-2) pathway to increase low-density lipoprotein receptor (LDLR) protein expression, alleviate lipid metabolism disorders, and regulate cholesterol and triglyceride levels. Conclusion Quantum lipid-lowering instrument has obvious effect of lipid regulation, and can be used as an assisted clinical instrument for lowering lipid.