MiR-145-5p modulates lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia

The present study aims to explore the role of microRNA 145-5p (miR-145-5p) in hyperlipidemia. Using bioinformatics tools and a wide range of function and mechanism assays, we attempted to understand the specific function and potential mechanism of miR-145-5p in hyperlipidemia. A cholesterol-enriched diet induced an increase of serum cholesterol and triacylglycerol but a decrease of serum high-density lipoprotein. MiR-145-5p level was decreased in hyperlipidemia rat models. MiR-145-5p regulated lipid metabolism by antagonizing the alteration of high-density lipoprotein, cholesterol, and triacylglycerol in serum mediated by a cholesterol-enriched diet. In mechanism, miR-145-5p directly bound with p21 protein (RAC1)-activated kinase 7 (PAK7) and negatively regulated mRNA and protein levels of PAK7 in THP-1 cells. Furthermore, miR-145-5p level was negatively associated with PAK7 level in rat cardiac tissues. Finally, overexpression of PAK7 reversed the effects of miR-145-5p on β-catenin activation and M2 macrophages polarization in THP-1 cells. In conclusion, MiR-145-5p modulated lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia, which may provide a potential biomarker for the treatment of hyperlipidemia-induced cardiovascular diseases.

Download Full-text

Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population

VASA ◽

10.1024/0301-1526/a000348 ◽

2014 ◽

Vol 43 (3) ◽

pp. 189-197 ◽

Cited By ~ 10

Author(s):

Yiqiang Zhan ◽

Jinming Yu ◽

Rongjing Ding ◽

Yihong Sun ◽

Dayi Hu

Keyword(s):

High Density Lipoprotein ◽

Total Cholesterol ◽

High Density Lipoprotein Cholesterol ◽

Ankle Brachial Index ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Cholesterol Ratio ◽

Potential Biomarker

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.

Download Full-text

Effect of fatty Amazon fish consumption on lipid metabolism

Revista de Nutrição ◽

10.1590/1415-52732014000100009 ◽

2014 ◽

Vol 27 (1) ◽

pp. 97-105 ◽

Cited By ~ 2

Author(s):

Francisca das Chagas do Amaral Souza ◽

Nadja Pinto Garcia ◽

Rejane Souza de Aquino Sales ◽

Jaime Paiva Lopes Aguiar ◽

Wallice Luiz Paxiúba Duncan ◽

...

Keyword(s):

Lipid Metabolism ◽

High Density Lipoprotein ◽

High Density Lipoprotein Cholesterol ◽

Amazon Basin ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Control Group ◽

Fatty Fish ◽

Serum Triglycerides

OBJECTIVE: The present study aimed to evaluate the effect of feeding diets enriched with fatty fish from the Amazon basin on lipid metabolism. METHODS: Male Wistar rats were divided into four groups: control group treated with commercial chow; Mapará group was fed diet enriched with Hypophthalmus edentatus; Matrinxã group was fed diet enriched with Brycon spp.; and, Tambaqui group was fed diet enriched with Colossoma macropomum. Rats with approximately 240g±0.60 of body weight were fed ad libitum for 30 days, and then were sacrificed for collection of whole blood and tissues. RESULTS: The groups treated with enriched diets showed a significant reduction in body mass and lipogenesis in the epididymal and retroperitoneal adipose tissues and carcass when compared with the control group. However, lipogenesis in the liver showed an increase in Matrinxã group compared with the others groups. The levels of serum triglycerides in the treated groups with Amazonian fish were significantly lower than those of the control group. Moreover, total cholesterol concentration only decreased in the group Matrinxã. High Density Lipoprotein cholesterol levels increased significantly in the Mapará and Tambaqui compared with control group and Matrinxã group. The insulin and leptin levels increased significantly in all treatment groups. CONCLUSION: This study demonstrated that diets enriched with fatty fish from the Amazon basin changed the lipid metabolism by reducing serum triglycerides and increasing high density lipoprotein-cholesterol in rats fed with diets enriched with Mapará, Matrinxã, and Tambaqui.

Download Full-text

Three routine methods for measuring high-density lipoprotein cholesterol compared with the Reference Method

Clinical Chemistry ◽

10.1093/clinchem/42.5.738 ◽

1996 ◽

Vol 42 (5) ◽

pp. 738-743 ◽

Cited By ~ 32

Author(s):

N Harris ◽

V Galpchian ◽

N Rifai

Keyword(s):

High Density Lipoprotein ◽

High Density Lipoprotein Cholesterol ◽

Dextran Sulfate ◽

Direct Method ◽

Density Lipoprotein ◽

Reference Method ◽

High Density ◽

Lipoprotein Cholesterol ◽

Direct Assay ◽

Wide Range

Abstract We compared the performance of three methods for quantifying high-density lipoprotein cholesterol (HDL-C) with the Reference Method for HDL-C, using samples with a wide range of triglyceride (TG) concentrations (290-18000 mg/L). All three comparison assays-- utilizing a magnetic dextran sulfate precipitating reagent, a direct method, and a standard MgCl2-dextran sulfate reagent--were precise, with a run-to-run CV of less than or equal to 4.1%. However, the systematic error of these assays exceeded the National Cholesterol Education Program (NCEP) performance goal of less than or equal to 10% in half of the concentration ranges tested. Nevertheless, the total error of the assays generally meets the current 22% limit set by the NCEP. Although both the magnetic dextran sulfate precipitation reagent and the direct assay can be performed more rapidly than the MgCl2-dextran sulfate assay, the direct assay involves no sample preparation and requires only 4 microL of sample excluding the dead space. Although precipitation is frequently inadequate with the MgCl2-dextran sulfate reagent at TG concentrations >6000 mg/L, both the magnetic and the direct reagent show no interference from high TG concentrations as great as 18 000 mg/L.

Download Full-text

Oral contraception in diabetic women. Diabetes control, serum and high density lipoprotein lipids during low-dose progestogen, combined oestrogen/progestogen and non-hormonal contraception

Acta Endocrinologica ◽

10.1530/acta.0.0980246 ◽

1981 ◽

Vol 98 (2) ◽

pp. 246-251 ◽

Cited By ~ 22

Author(s):

Thomas Rådberg ◽

Anders Gustafson ◽

Asbjörn Skryten ◽

Kirsten Karlsson

Keyword(s):

Body Weight ◽

Lipid Metabolism ◽

High Density Lipoprotein ◽

Density Lipoprotein ◽

Insulin Requirement ◽

High Density ◽

Diabetes Control ◽

Insulin Dosage ◽

Urinary Glucose ◽

Insulin Dependent

Abstract. Thirtyeight women with insulin-dependent diabetes were randomly allocated to contraception with either a progestogen only (Lynestrenol 0.5 mg daily) (LYN), a combined oral contraceptive (OC) (Ethinyl oestradiol 50 μg + Lynestrenol 2.5 mg) (EE + LYN) or a non-hormonal intrauterine device (IUD). Diabetes control (i.e. insulin dosage, blood and urinary glucose and body weight) and the lipid concentration in serum and in high density lipoprotein (HDL) were assessed before and during six months use of the respective contraceptives. In the LYN group urinary glucose excretion increased 10% in spite of unchanged blood glucose, body weight and insulin requirement. All serum lipids decreased; triglycerides by 40% (P < 0.01), cholesterol by 13% (P < 0.01) and phospholipids by 12% (P = 0.06), without alteration of HDL lipids. In the group using combined OC (EE + LYN) the insulin requirement increased by 7% (P < 0.01) without any change in body weight or blood and urinary glucose. Serum as well as HDL lipids remained unchanged. In the IUD group neither diabetes control nor serum or HDL lipids were altered. It is concluded that in insulin-dependent diabetics the progestogen (LYN) has little influence on diabetes control but has a marked, though probably not adverse, effect on lipid metabolism. The combined OC (EE + LYN) may impair glucose homeostasis slightly but has little influence on serum or HDL lipids. These findings seem to differ from those obtained in non-diabetics during administration of contraceptive steroids and these differences suggest that absence of endogenous insulin production enhances the effects of progestogen and reduces the effects of synthetic oestrogens on lipid metabolism.

Download Full-text