循环血管生成素样蛋白 8 水平升高与胸主动脉夹层和更高的炎症状态相关。
Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions.
机构信息
Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Capital Medical University, 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing An Zhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Capital Medical University, Beijing, 100029, China.
出版信息
Cardiovasc Drugs Ther. 2020 Feb;34(1):65-77. doi: 10.1007/s10557-019-06924-7.
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）的特征是炎症反应。血管生成素样蛋白 8（ANGPTL8）是一种参与脂质代谢和炎症调节的激素。然而，ANGPTL8 与 TAD 之间的关系尚不清楚。
方法
本病例对照研究纳入了 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。通过酶联免疫吸附试验测量循环 ANGPTL8 水平。通过多变量逻辑回归确定 ANGPTL8 与 TAD 的相关性。
结果
与对照组相比，TAD 患者的血清 ANGPTL8 水平显著升高（分别为 562.50±20.84 pg/mL 和 419.70±22.65 pg/mL；P<0.001）。在校正混杂因素后，循环 ANGPTL8 水平是 TAD 的独立危险因素（比值比=1.587/100 pg ANGPTL8，95%置信区间[CI]：1.121-2.247，P<0.001），并与直径呈正相关（β=1.081/100 pg ANGPTL8，95%CI：0.075-2.086，P=0.035）和高敏 C 反应蛋白（hs-CRP）（β=0.845/100 pg ANGPTL8，95%CI：0.020-1.480，P=0.009）。接受者操作特征（ROC）曲线分析中 ANGPTL8、hs-CRP 和 D-二聚体联合的曲线下面积（AUC）为 0.927，特异性和敏感性分别为 98.46%和 79.49%。TAD 组织中 ANGPTL8 明显高于对照组。体外，血管紧张素 II（AngII）处理的巨噬细胞和血管平滑肌细胞（VSMCs）中 ANGPTL8 增加，而 AngII 处理的巨噬细胞中 ANGPTL8 siRNA 介导的敲低降低了炎症因子，AngII 处理的 VSMCs 中降低了细胞凋亡。
结论
ANGPTL8 与 TAD 的发生和发展有关，可能涉及对巨噬细胞的促炎作用。ANGPTL8 联合 D-二聚体和 hs-CRP 可能是 TAD 的一种有用的临床预测指标。
试验注册
ChiCTR-COC-17010792 http://www.chictr.org.cn/showproj.aspx?proj=18288。
Zotero 插件