关键词: Chronic kidney disease Diagnostic biomarker Uremic Vascular calcification

Mesh : Humans Hyperphosphatemia / complications metabolism pathology Inflammation / genetics metabolism Kidney Failure, Chronic / genetics Myocytes, Smooth Muscle / metabolism Oxidative Stress / genetics Renal Insufficiency, Chronic / genetics RNA, Long Noncoding / genetics metabolism Vascular Calcification / genetics metabolism

来  源:   DOI:10.1016/j.gene.2023.148035

Abstract:
OBJECTIVE: Vascular calcification is a frequently occurring complication of end-stage renal disease (ESRD). This study focused on the significance of long non-coding RNA Fas cell surface death receptor-antisense 1(lncRNA FAS-AS1) in ESRD-related vascular calcification aiming to explore a potential biomarker for the detection.
METHODS: The study enrolled 65 healthy individuals, 79 ESRD patients (48 patients with vascular calcification), and 93 early-stage (I-IV) chronic kidney disease (CKD) patients. The expression of FAS-AS1 in serum was evaluated by real-time quantitative polymerase chain reaction (PCR). The diagnostic potential of FAS-AS1 was assessed in discriminating ESRD patients, vascular calcification, and the severity of vascular calcification. In vitro, the vascular smooth muscle cells (VSMCs) were treated with a hyperphosphatemia medium to evaluate the effect of FAS-AS1 on VSMCs calcification.
RESULTS: Elevated serum FAS-AS1 was observed in ESRD patients, which could discriminate from healthy individuals and early-stage CKD patients. FAS-AS1 was associated with the development of ESRD and the occurrence of vascular calcification. FAS-AS1 was also upregulated in vascular calcification patients, especially the patients with severe calcification, which showed diagnostic significance in evaluating vascular calcification degrees. Calcified VSMCs showed significantly increased levels of Ca2+, reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), which was attenuated by silencing FAS-AS1.
CONCLUSIONS: FAS-AS1 discriminated ERSD patients and was associated with the occurrence of vascular calcification. The knockdown of FAS-AS1 suppressed hyperphosphatemia-induced vascular calcification via alleviating oxidative stress and inflammation.
摘要:
目的:血管钙化是终末期肾病(ESRD)的常见并发症。这项研究集中于长链非编码RNAFas细胞表面死亡受体反义1(lncRNAFAS-AS1)在ESRD相关血管钙化中的意义,旨在探索检测的潜在生物标志物。
方法:该研究招募了65名健康个体,79例ESRD患者(血管钙化48例),和93例早期(I-IV)慢性肾脏病(CKD)患者。实时定量聚合酶链反应(PCR)检测血清中FAS-AS1的表达。FAS-AS1的诊断潜力在区分ESRD患者中进行了评估,血管钙化,血管钙化的严重程度。体外,用高磷酸盐血症培养基处理血管平滑肌细胞(VSMC),以评估FAS-AS1对VSMC钙化的影响.
结果:在ESRD患者中观察到血清FAS-AS1升高,可以区分健康个体和早期CKD患者。FAS-AS与ESRD的发生、血管钙化的发生有关。FAS-AS1在血管钙化患者中也上调,尤其是严重钙化的患者,对评价血管钙化程度具有诊断意义。钙化的VSMC显示Ca2+水平显著升高,活性氧(ROS),肿瘤坏死因子-α(TNF-α),和白细胞介素6(IL-6),通过沉默FAS-AS1减弱。
结论:FAS-AS1可区分ERSD患者,并与血管钙化的发生有关。FAS-AS1的敲减通过减轻氧化应激和炎症抑制高磷血症诱导的血管钙化。
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