Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions.
循环血管生成素样蛋白 8 水平升高与胸主动脉夹层和较高的炎症状况相关。
- 作者列表："Yang Y","Jiao X","Li L","Hu C","Zhang X","Pan L","Yu H","Li J","Chen D","Du J","Qin Y
PURPOSE:Thoracic aortic dissection (TAD) is characterized by an inflammatory response. Angiopoietin-like protein 8 (ANGPTL8) is a hormone involved in the regulation of lipid metabolism and inflammation. However, the relationship between ANGPTL8 and TAD remains unknown. METHODS:This case-control study included 78 TAD patients and 72 controls. The aortic diameter was evaluated by computed tomography and used to assess TAD severity. Circulating ANGPTL8 levels were measured by enzyme-linked immunosorbent assay. Associations of ANGPTL8 with TAD were determined by multivariate logistic regression. RESULTS:Serum ANGPTL8 levels were significantly higher in TAD patients compared with controls (562.50 ± 20.84 vs. 419.70 ± 22.65 pg/mL, respectively; P < 0.001). After adjusting for confounding factors, circulating ANGPTL8 levels were an independent risk factor for TAD (odds ratio = 1.587/100 pg ANGPTL8, 95% confidence interval [CI] = 1.121-2.247, P < 0.001) and positively associated with diameter (β = 1.081/100 pg ANGPTL8, 95% CI = 0.075-2.086, P = 0.035) and high-sensitivity C-reactive protein (hs-CRP) (β = 0.845/100 pg ANGPTL8, 95% CI = 0.020-1.480, P = 0.009). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8, hs-CRP, and D-dimer was 0.927, and the specificity and sensitivity were 98.46% and 79.49%, respectively. ANGPTL8 was significantly increased in TAD tissue compared with controls. In vitro, ANGPTL8 was increased in angiotensin II (AngII)-treated macrophages and vascular smooth muscle cells (VSMCs), while ANGPTL8 siRNA-mediated knockdown decreased inflammatory factors in AngII-treated macrophages and decreased apoptosis in AngII-treated VSMCs. CONCLUSION:ANGPTL8 is associated with TAD occurrence and development, which may involve pro-inflammatory effects on macrophages. ANGPTL8 combined with D-dimer and hs-CRP might be a useful clinical predictor of TAD. TRIAL REGISTRATION:ChiCTR-COC-17010792 http://www.chictr.org.cn/showproj.aspx?proj=18288.
目的: 胸主动脉夹层 (TAD) 以炎症反应为特征。血管生成素样蛋白 8 (ANGPTL8) 是一种参与调节脂质代谢和炎症的激素。然而，ANGPTL8 和 TAD 之间的关系仍然未知。 方法: 本病例对照研究包括 78 例 TAD 患者和 72 例对照。通过计算机断层扫描评估主动脉直径，并用于评估 TAD 严重程度。采用酶联免疫吸附法测定循环 ANGPTL8 水平。通过多因素 logistic 回归确定 ANGPTL8 与 TAD 的相关性。 结果: TAD 患者血清 ANGPTL8 水平显著高于对照组 (分别为 562.50 ± 20.84 vs.419.70 ± 22.65 pg/mL; p
METHODS:BACKGROUND:Given the importance of habitual dietary protein intake, distribution patterns and dietary sources in the aetiology of age-related declines of muscle mass and function, the present study examined these factors as a function of sex and age in Irish adults aged 18-90 years comprising The National Adult Nutrition Survey (NANS). METHODS:In total, 1051 (males, n = 523; females, n = 528) undertook a 4-day semi-weighed food diary. Total, body mass relative intake and percentage contribution to total energy intake of dietary protein were determined in addition to protein distribution scores (PDS), as well as the contribution of food groups, animal- and plant-based foods to total protein intake. RESULTS:Total and relative protein intake [mean (SD)] were highest in those aged 18-35 years [96 (3) g day , 1.32 (0.40) g kg day ], with lower protein intakes with increasing age (i.e. in adults aged ≥65 years [82 (22) g, 1.15 (0.34) g kg day , P < 0.001 for both]. Differences in protein intake between age groups were more pronounced in males compared to females. Protein distribution followed a skewed pattern for all age groups [breakfast, 15 (10) g; lunch, 30 (15) g; dinner, 44 (17) g]. Animal-based foods were the dominant protein source within the diet [63% (11%) versus 37% (11%) plant protein, P < 0.001]. CONCLUSIONS:Protein intake and the number of meals reaching the purported threshold for maximising post-prandial anabolism were highest in young adults, and lower with increasing age. For main meals, breakfast provided the lowest quantity of protein across all age categories and may represent an opportunity for improving protein distribution, whereas, in older adults, increasing the number of meals reaching the anabolic threshold regardless of distribution pattern may be more appropriate.
METHODS:BACKGROUND:Low cardiorespiratory fitness (CRF) increases risk of all-cause mortality and cardiovascular events. Periodic CRF assessment can have an important preventive function. OBJECTIVE:To develop a protocol-free method to estimate CRF in daily life based on heart rate (HR) and body acceleration measurements. METHODS:Acceleration and HR data were collected from 37 subjects (M=49%) while performing a standardized laboratory activity protocol (sitting, walking, running, cycling) and during a 5-days free-living monitoring period. CRF was determined by oxygen uptake (VO2max) during maximal exercise testing. A doubly-labeled water validated equation was used to predict total energy expenditure (TEE) from acceleration data. A fitness index was defined as the ratio between TEE and HR (TEE-pulse). Activity recognition techniques were used to process acceleration features and classify sedentary, ambulatory and other activity types. Regression equations based on TEE-pulse data from each activity type were developed to predict VO2max. RESULTS:TEE-pulse measured within each activity type of the laboratory protocol was highly correlated to VO2max (r from 0.74 to 0.91). Averaging the outcome of each activity-type specific equation based on TEE-pulse from the laboratory data led to accurate estimates of VO2max (RMSE: 300.0 mlO2/min or 10%). The difference between laboratory and free-living determined TEE-pulse was 3.7 ± 11% (r =0.85). The prediction method preserved the prediction accuracy when applied to free-living data (RMSE: 367 mlO2/min or 12%). CONCLUSIONS:Measurements of body acceleration and HR can be used to predict VO2max in daily life. Activity-specific prediction equations are needed to achieve highly accurate estimates of CRF.
METHODS:OBJECTIVE:Postprandial dyslipidemia is a common feature of insulin resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. While bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Approach and Results: Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and with deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA effects (but not DCA) were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the anti-diabetic hormone glucagon-like peptide-1 (GLP-1). While the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate limiting enzyme for bile acid synthesis. CONCLUSIONS:Bile acid signaling may be an important mechanism of controlling dietary lipid absorption and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.