Association between PCSK9 Levels and Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction in a Population of Nondialysis Chronic Kidney Disease Patients.
Association between PCSK9 Levels and Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction in a Population of Nondialysis Chronic Kidney Disease Patients.
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DOI：
10.1155/2021/6677012
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发表时间：
2021
影响因子：
--
通讯作者：
Tselepis AD
中科院分区：
文献类型：
--
作者：
Dounousi E;Tellis C;Pavlakou P;Duni A;Liakopoulos V;Mark PB;Papagianni A;Tselepis AD
前蛋白转化酶枯草杆菌蛋白酶 9 (PCSK9) 在脂质代谢中发挥着重要作用，而有关其参与动脉粥样硬化发病机制以及与细胞凋亡和炎症相关基因表达的现有文献不断增加。由于血脂异常、动脉粥样硬化加速、炎症、氧化应激和其他危险因素，慢性肾脏病 (CKD) 患者的心血管发病率和死亡率不成比例地增加。在本横断面研究中，我们研究了 CKD 患者血清 PCSK9 水平与炎症、氧化应激和内皮损伤标志物的可能关联。患者和方法。该研究纳入了 92 名 CKD II-IV 期患者（eGFR CKD-EPI 47.3 ± 25.7ml/min/1.73m2，平均年龄 66 岁，51 名男性）。血浆 PCSK9 水平与合并症（高血压、糖尿病和心血管疾病史）、肾功能指数（eGFR、蛋白尿–UPR/24 h）、脂质参数（LDL-胆固醇、HDL-胆固醇、甘油三酯、Lp(a)、APO-A1 和 APO-B）以及炎症、氧化应激和内皮损伤的可溶性生物标志物相关（hs-CRP、纤维蛋白原、8-epiPGF2a、ox-LDL、IL-6、TNF-α、sICAM-1 和 sVCAM-1）。结果。 PCSK9的平均血浆值为278.1ng/ml。 PCSK9 水平与血清甘油三酯 (p = 0.03)、Lp(a) (p = 0.01) 和 sICAM-1 水平 (p = 0.03) 直接相关。 PCSK9 水平与肾功能指数、其他血脂参数、炎症标志物或合并症之间没有显着相关性。多元回归分析显示 Lp(a) 对 PCSK9 水平有显着影响，并且 Lp(a) 每升高一个单位，预计会增加 3.082（95% CI：0.935-5.228，p = 0.006）。同时，与未接受他汀类药物的患者相比，接受他汀类药物的患者预计 PCSK9 值平均高出 63.8ng/ml（95% CI：14.6-113.5，p = 0.012）。结论。非透析 CKD 患者的血浆 PCSK9 水平与内皮功能障碍和脂质代谢参数相关。他汀类药物的摄入量显着增加了该患者群体中的 PCSK9 水平。 PCSK9 水平与肾脏疾病的严重程度无关。需要进行大型前瞻性研究来调查 PCSK9 在 CKD 动脉粥样硬化心血管结局中的作用。
Proprotein convertase subtilisin/kexin 9 (PCSK9) plays an important role in lipid metabolism while available literature regarding its involvement in the pathogenesis of atherosclerosis and in the expression of genes associated with apoptosis and inflammation is constantly increasing. Patients with chronic kidney disease (CKD) experience disproportionately increased cardiovascular morbidity and mortality due to dyslipidemia, accelerated atherosclerosis, inflammation, oxidative stress, and other risk factors. In the present cross-sectional study, we investigated the possible association of serum PCSK9 levels with markers of inflammation, oxidative stress, and endothelial damage in patients with CKD. Patients and Methods. Ninety-two patients with CKD stages II-ΙV (eGFR CKD-EPI 47.3 ± 25.7 ml/min/1.73 m2, mean age 66 years, 51 men) were included in the study. Plasma PCSK9 levels were correlated with comorbidities (arterial hypertension, diabetes mellitus, and history of cardiovascular disease), renal function indices (eGFR, proteinuria–UPR/24 h), lipid parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), APO-A1, and APO-B), and soluble biomarkers of inflammation, oxidative stress, and endothelial damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-α, sICAM-1, and sVCAM-1). Results. The mean plasma value of PCSK9 was 278.1 ng/ml. PCSK9 levels showed direct correlation with serum triglycerides (p = 0.03), Lp(a) (p = 0.01), and sICAM-1 levels (p = 0.03). There was no significant correlation between PCSK9 levels and indices of the renal function, other lipid profile parameters, inflammatory markers, or comorbidities. Multiple regression analysis showed a significant effect of Lp(a) on PCSK9 levels, and for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: 0.935-5.228, p = 0.006). At the same time, patients receiving statins are expected to have on average 63.8 ng/ml higher PCSK9 values compared to patients not receiving statins (95% CI: 14.6-113.5, p = 0.012). Conclusion. Plasma levels of PCSK9 in nondialysis CKD patients are correlated with endothelial dysfunction and lipid metabolism parameters. Statin intake increases PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated with the severity of kidney disease. Major prospective studies are necessary to investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD.
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影响因子：
39.3
作者：
Landlinger C;Pouwer MG;Juno C;van der Hoorn JWA;Pieterman EJ;Jukema JW;Staffler G;Princen HMG;Galabova G
通讯作者：
Galabova G
影响因子：
6.5
作者：
Kühnast S;van der Hoorn JW;Pieterman EJ;van den Hoek AM;Sasiela WJ;Gusarova V;Peyman A;Schäfer HL;Schwahn U;Jukema JW;Princen HM
通讯作者：
Princen HM
影响因子：
1.9
作者：
Kostapanos, Michael S.;Spyrou, Athanasia T.;Liberopoulos, Evangelos N.
通讯作者：
Liberopoulos, Evangelos N.
影响因子：
3.4
作者：
Li J;Liang X;Wang Y;Xu Z;Li G
通讯作者：
Li G
影响因子：
39.3
作者：
Gencer, Baris;Montecucco, Fabrizio;Mach, Francois
通讯作者：
Mach, Francois