[1]李 强,邢慧敏,范海超,等.射血分数保留心力衰竭患者血清WWP1 和NLRP3 的表达水平及其临床价值研究[J].现代检验医学杂志,2024,39(02):151-156.[doi:10.3969/j.issn.1671-7414.2024.02.028]
 LI Qiang,XING Huimin,FAN Haichao,et al.Study on Serum WWP1 and NLRP3 Expression Levels and Their Clinical Value in Patients with Heart Failure with Preserved Ejection Fraction[J].Journal of Modern Laboratory Medicine,2024,39(02):151-156.[doi:10.3969/j.issn.1671-7414.2024.02.028]
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射血分数保留心力衰竭患者血清WWP1 和NLRP3 的表达水平及其临床价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年02期
页码:
151-156
栏目:
论著
出版日期:
2024-03-31

文章信息/Info

Title:
Study on Serum WWP1 and NLRP3 Expression Levels and Their Clinical Value in Patients with Heart Failure with Preserved Ejection Fraction
文章编号:
1671-7414(2024)02-151-06
作者:
李 强邢慧敏范海超李 玲
(华北医疗健康集团峰峰总医院心内一科,河北邯郸 056200)
Author(s):
LI Qiang XING Huimin FAN Haichao LI Ling
(Department 1 of Cardiology, Fengfeng General Hospital of North China Medical and Health Group, Hebei Handan 056200, China)
关键词:
射血分数保留心力衰竭WW 结构域E3 泛素蛋白连接酶1核苷酸结合寡聚化结构域样受体蛋白3
分类号:
R541.6;R446.11
DOI:
10.3969/j.issn.1671-7414.2024.02.028
文献标志码:
A
摘要:
目的 探讨WW 结构域E3 泛素蛋白连接酶1(WW domain-containing E3 ubiquitin protein ligase 1,WWP1)和核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)在射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)患者血清中的表达水平及临床意义。方法 选取华北医疗健康集团峰峰总医院2021 年1 月~ 2022 年9 月收治的153 例HFpEF 患者为观察组,并根据患者纽约心脏病协会(New York Heart Association,NYHA)心功能分级分为心功能分级I ~ II 级组(n=64)和心功能分级III ~ IV 级组(n=89),另选取同期体检健康的148 例志愿者为对照组。血清WWP1,NLRP3 水平与患者心功能指标的相关性采用Pearson 分析;受试者工作特征(receiver operating characteristic,ROC)曲线分析血清WWP1 和NLRP3水平对HFpEF 患者心衰严重程度的诊断价值。结果 与对照组比较,观察组血清WWP1(1.68 ± 0.35 vs 1.04 ± 0.19)和NLRP3(6.72 ± 1.26 ng/ml vs 4.57 ± 0.84 ng/ml)表达水平明显升高,差异具有统计学意义(t=19.623,17.359,均P < 0.05);与心功能分级I ~ II 级组比较,心功能分级III ~ IV 级组血清WWP1(1.87 ± 0.39 vs 1.42 ± 0.32)和NLRP3(7.53 ± 1.40 ng/ml vs 5.59 ± 1.18 ng/ml)表达水平明显升高,差异具有统计学意义(t=7.744,9.017,均P< 0.05);心功能分级I ~ II 级组与心功能分级III ~ IV 级组心率、左心房内径(left atrial diameter,LAD)、左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)、左室舒张末期后壁厚度(left ventricular end-diastolicposterior wall thickness,LVPWT)、左心室射血分数(left ventricular ejection fraction,LVEF)、二尖瓣舒张早期流速峰值(peak mitral early diastolic velocity,E)/ 舒张晚期流速峰值(peak late diastolic velocity,A)以及心房颤动发生率比较差异均具有统计学意义(t/χ2=2.757 ~ 7.069,均P < 0.05);HFpEF 患者血清WWP1 水平与LAD,LVEDD,LVPWT 呈正相关(r=0.547,0.471,0.536,均P < 0.05),与LVEF 和E/A 呈负相关(r=-0.485,-0.417,均P < 0.05);血清NLRP3 水平与LAD,LVEDD,LVPWT 呈正相关(r=0.534,0.494,0.520,均P < 0.05),与LVEF 和E/A 呈负相关(r=-0.462,-0.523,均P < 0.05)。ROC 结果显示,血清WWP1 和NLRP3 水平单独诊断HFpEF 患者心衰严重程度的曲线下面积(area under the curve,AUC)分别为0.825 和0.855,两者联合诊断的AUC(0.924)显著大于血清WWP1 和NLRP3 水平单独诊断的AUC(Z=3.600,P<0.001;Z=3.053,P=0.002)。结论 血清WWP1 和NLRP3 水平在HFpEF 患者中明显升高,且与患者心功能密切相关,血清WWP1 和NLRP3 对HFpEF 患者心衰严重程度具有一定的诊断价值。
Abstract:
Objective To investigate the expression level and clinical significance of WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in patients with heart failure with preserved ejection fraction (HFpEF). Methods A total of 153 patients with HFpEF admitted to Fengfeng General Hospital of North China Medical and Health Group from January 2021 to September 2022 were collected as the observation group. According to the New York Heart Association (NYHA) cardiac function grading of patients, they were grouped into cardiac function grading I ~ II group (n=64) and cardiac function grading III ~ IV group (n=89), while 148 healthy volunteers were collected as the control group. The correlation between serum WWP1 and NLRP3 levels and cardiac function indexes of patients was explored by Pearson analysis. The diagnostic value of serum WWP1 and NLRP3 levels on the severity of heart failure in HFpEF patients was analyzed by the receiver operating characteristic (ROC) curve. Results Compared with the control group, the expression levels of WWP1 (1.68 ± 0.35 vs 1.04 ± 0.19) and NLRP3 (6.72 ± 1.26 ng/ml vs 4.57 ± 0.84 ng/ ml) in the observation group were significantly increased,and the differences were statistically significant (t=19.623, 17.359, all P < 0.05). Compared with grade I to II groups, WWP1 (1.87 ± 0.39 vs 1.42 ± 0.32) and NLRP3 (7.53 ± 1.40 ng/ml vs 5.59 ± 1.18 ng/ml) expression levels in grade III to IV groups were significantly increased and the differences were statistically significant (t=7.744, 9.017, all P < 0.05). The differences of heart rate, left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic posterior wall thickness (LVPWT), left ventricular ejection fraction (LVPWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic velocity (E) / peak late diastolic velocity (A) and the incidence of atrial fibrillation between the cardiac function grade I to II groups and the grade III to IV groups were significant (t/ χ2=2.757 ~ 7.069, all P < 0.05). Serum WWP1 level in HFpEF patients was positively correlated with LAD, LVEDD and LVPWT (r=0.547, 0.471, 0.536, all P < 0.05), and negatively correlated with LVEF and E/A (r=-0.485, -0.417, all P < 0.05). Serum NLRP3 level was positively correlated with LAD, LVEDD and LVPWT (r=0.534, 0.494, 0.520, all P < 0.05), and negatively correlated with LVEF and E/A (r=-0.462, -0.523, all P < 0.05). ROC results showed that the area under the curve (AUC) of serum WWP1 and NLRP3 levels alone for diagnosing the severity of heart failure in HFpEF patients was 0.825 and 0.855, respectively, and the AUC (0.924) diagnosed by the combination of the two was significantly greater than that diagnosed by the serum WWP1 alone and the AUC diagnosed by the NLRP3 alone (Z=3.600,P<0.001;Z=3.053,P=0.002). Conclusion The levels of serum WWP1 and NLRP3 were increased in patients with HFpEF, which were closely related to the cardiac function of patients. Serum WWP1 and NLRP3 have certain diagnostic value for the severity of heart failure in patients with HFpEF.

参考文献/References:

[1] ELTELBANY M, SHAH P, DE FILIPPI C. Biomarkers in HFpEF for diagnosis, prognosis, and biological phenotyping[J]. Current Heart Failure Reports, 2022,19(6): 412-424.
[2] BORLAUG B A. Evaluation and management of heart failure with preserved ejection fraction[J]. Nature Reviews Cardiology, 2020, 17(9): 559-573.
[3] 张丽伟, 李晓丹, 赵赫, 等. 射血分数正常心力衰竭患者Fibrosis-4 指数与右心室功能及预后的相关性研究[J]. 现代检验医学杂志, 2022, 37(2): 167-172. ZHANG Liwei, LI Xiaodan, ZHAO He, et al. Correlation between Fibrosis 4 index and right ventricular function and prognosis in patients with heart failure with preserved ejection fraction[J]. Journal of Modern Laboratory Medicine, 2022, 37(2): 167-172.
[4] JIN Xuanyi, NAUTA J F, HUNG C L, et al. Left atrial structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF):systematic review and meta-analysis[J]. Heart Failure Reviews, 2022, 27(5): 1933-1955.
[5] PAGEL P S, TAWIL J N, BOETTCHER B T, et al. Heart failure with preserved ejection fraction:a comprehensive review and update of diagnosis,pathophysiology, treatment, and perioperative implications[J]. Journal of Cardiothoracic and Vascular Anesthesia, 2021, 35(6): 1839-1859.
[6] ZHAO Dingsheng, ZHONG Guohui, LI Jianwei, et al. Targeting E3 ubiquitin ligase WWP1 prevents cardiac hypertrophy through destabilizing DVL2 via inhibition of K27-linked ubiquitination[J]. Circulation, 2021,144(9): 694-711.
[7] ZHANG Jie, LIU Xinqiang, WAN Chunyan, et al. NLRP3 inflammasome mediates M1 macrophage polarization and IL-1β production in inflammatory root resorption[J]. Journal of Clinical Periodontology,2020, 47(4): 451-460.
[8] ZHANG Shuyao, GUAN Xinmin, LIU Wei, et al. YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis[J]. Cell Death Discovery, 2022,8(1): 244.
[9] 中华医学会心血管病学分会心力衰竭学组, 中国医师协会心力衰竭专业委员会, 中华心血管病杂志编辑委员会. 中国心力衰竭诊断和治疗指南2018[J].中华心血管病杂志, 2018, 46(10): 760-789. Heart Failure Group of Chinese Society of Cardiology of Chinese Medical Association, Chinese Heart Failure Association of Chinese Medical Doctor Association,Editorial Board of Chinese Journal of Cardiology. Chinese guidelines for the diagnosis and treatment of heart failure 2018[J]. Chinese Journal of Cardiology,2018, 46(10): 760-789.
[10] 屈慧, 李娅, 黄瑶楠, 等. 心力衰竭患者外周血RDW和NT-pro-BNP 联合检测对临床诊断及分级的相关性研究[J]. 现代检验医学杂志, 2020, 35(5): 65-67,72. QU Hui, LI Ya, HUANG Yaonan, et al. Correlation study on the combined detection of RDW and NT-Pro-BNP in patients with heart failure to clinical diagnosis and grading[J].Journal of Modern Laboratory Medicine,2020, 35(5): 65-67, 72.
[11] WITHAAR C, MEEMS L M G, MARKOUSISMAVROGENIS G, et al. The effects of liraglutide and dapagliflozin on cardiac function and structure in a multi-hit mouse model of heart failure with preserved ejection fraction[J]. Cardiovascular Research, 2021,117(9): 2108-2124.
[12] HEATH R, JOHNSEN H, STRAIN W D, et al. Emerging horizons in heart failure with preserved ejection fraction: the role of SGLT2 inhibitors[J].Diabetes Therapy, 2022, 13(2): 241-250.
[13] 张成伟, 毕昕, 闫睿, 等. 敲低WWP1 对肺癌SPCA1细胞增殖和侵袭能力影响及其机制[J]. 中华肿瘤防治杂志, 2021, 28(16): 1203-1208. ZHANG Chengwei, BI Xin, YAN Rui, et al. Effect of knockdown of WWP1 on the proliferation and invasion of lung cancer SPC-A1 cells and its mechanism[J].Chinese Journal of Cancer Prevention and Treatment,2021, 28(16): 1203-1208.
[14] SNYDER L B, LAI Yimu, DOVIAK H, et al. Ubiquitin ligase Wwp1 gene deletion attenuates diastolic dysfunction in pressure-overload hypertrophy[J].American Journal of Physiology. Heart and Circulatory Physiology, 2021, 321(5): H976-H984.
[15] LU Xia, YANG Boshen, QI Ruiqiang, et al. Targeting WWP1 ameliorates cardiac ischemic injury by suppressing KLF15-ubiquitination mediated myocardial inflammation[J]. Theranostics, 2023, 13(1): 417-437.
[16] 焦雪, 黄树宣. 基于NLRP3 炎症小体复合物为靶点的帕金森病治疗研究新进展[J]. 中国临床新医学,2022, 15(12): 1123-1129. JIAO Xue, HUANG Shuxuan. New advances in therapy of Parkinson’s disease based on NLRP3 inflammasome[J]. Chinese Clinical of New Clinical Medicine, 2022, 15(12): 1123-1129.
[17] 刘艳, 史伟东. 老年慢性心力衰竭患者血清miR-223, NLRP3 水平与心肌重构及心功能的相关性[J].海南医学, 2022, 33(19): 2471-2475. LIU Yan, SHI Weidong. Correlation of serum microRNA-233 and NOD-like receptor protein 3 levels with myocardial remodeling and cardiac function in elderly patients with chronic heart failure[J]. Hainan Medical Journal, 2022, 33(19): 2471-2475.
[18] 田丽. 钙调控蛋白参与的NLRP3 炎症小体激活在高血压所致射血分数保留的心力衰竭中的作用机制研究[D]. 兰州:兰州大学, 2022. TIAN Li. Study on the mechanism of calcium regulatory protein involving in NLRP3 inflammasome activation in heart failure with preserved ejection fraction induced by hypertension[D]. LAN Zhou:Lanzhou University, 2022.
[19] GUO Lizhe, QIN Gang, CAO Yanan, et al. Regulation of the immune microenvironment by an NLRP3 inhibitor contributes to attenuation of acute right ventricular failure in rats with pulmonary arterial hypertension[J]. Journal of Inflammation Research,2021, 14: 5699-5711.

备注/Memo

备注/Memo:
基金项目: 邯郸市科学技术研究与发展计划项目(编号:19422083012-13):血清高敏肌钙蛋白T,sST-2 水平变化在射血分数保留心力衰竭患者预后评估中的价值。
作者简介:李强(1975-),男,本科,主治医师,研究方向:冠心病与心力衰竭,E-mail:g1fnj3fa@163.com。
通讯作者:付静静(1989-),女,研究生,主治医师,研究方向:心力衰竭与心脏电生理,E-mail:irbing412798@163.com。
更新日期/Last Update: 2024-03-15