血管生成素样蛋白 4、载脂蛋白 C3 和脂蛋白脂肪酶轴在类风湿关节炎患者中被破坏。
The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupted in patients with rheumatoid arthritis.
机构信息
Division of Health Sciences, Universidad Europea de Canarias, Tenerife, Spain.
Division of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, Spain.
出版信息
Arthritis Res Ther. 2022 Apr 29;24(1):99. doi: 10.1186/s13075-022-02784-z.
BACKGROUND
Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA.
METHODS
Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis.
RESULTS
Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213-376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7-4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. -174 [95% CI -213 to -135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment.
CONCLUSION
The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.
背景
甘油三酯代谢调节剂包括脂蛋白脂肪酶（LPL）、血管生成素样蛋白 4（ANGPTL4）和载脂蛋白 C-3（ApoC3）。有证据表明，这三种分子的相互作用会增加普通人群患动脉粥样硬化性心血管疾病（CV）的风险。类风湿关节炎（RA）患者的血脂谱发生变化，CV 疾病加速。在本研究中，我们着手研究 RA 患者与对照组相比，ANGPTL4、ApoC3 和 LPL 轴是否存在差异。在进一步的步骤中，我们研究了该轴与 RA 患者亚临床动脉粥样硬化的关系。
方法
这是一项横断面研究，共纳入 569 人，其中 323 名 RA 患者和 246 名年龄匹配的对照组。分析了患者和对照组的 ANGPTL4、ApoC3 和 LPL 以及标准血脂谱。在 RA 患者中评估了颈动脉内膜中层厚度（cIMT）和颈动脉斑块。进行多变量分析以评估 RA 中 ANGPTL4、ApoC3 和 LPL 轴是否发生改变，并研究其与 RA 血脂异常和亚临床颈动脉粥样硬化的关系。
结果
患者和对照组之间大多数血脂谱分子没有差异。尽管如此，在包括 CV 危险因素、他汀类药物的使用以及疾病本身引起的血脂谱变化在内的全多变量分析后，RA 患者的血清 ANGPTL4 水平更高（β系数 295[95%CI 213-376]ng/ml，p<0.001）和 ApoC3（β系数 2.9[95%CI 1.7-4.0]mg/dl，p<0.001），但循环 LPL 水平较低（β系数-174[95%CI -213 至-135]ng/ml，p<0.001）。在全多变量调整后，血清 ANGPTL4 水平与 RA 患者更高的 cIMT 呈正相关且独立相关。
结论
RA 患者的 ANGPTL4、ApoC3 和 LPL 轴发生紊乱。血清 ANGPTL4 水平与 RA 患者更高的 cIMT 呈正相关且独立相关。
Zotero 插件