Relationship between serum cathepsin K and ADAMTS-7 with ventricular remodeling and prognosis in patients with chronic heart failure

doi:10.3969/j.issn.1673-8640.2023.10.003

Abstract

Abstract:

Objective To investigate the relationship between serum cathepsin K（Cat-K） and a disintegrin and metalloproteinase with thrombospondin motifs 7（ADAMTS-7） with ventricular remodeling and prognosis in chronic heart failure（CHF） patients. Methods Totally，195 patients with CHF（CHF group） and 101 healthy subjects（control group） were enrolled from Handan Central Hospital from February 2018 to June 2020. The general data of CHF patients were collected. Random blood glucose，glycated hemoglobin A_1c（HbA_1c），N-terminal pro-B-type natriuretic peptide（NT-proBNP），B-type natriuretic peptide（BNP），Cat-K and ADAMTS-7 levels and left ventricular ejection fraction（LVEF），ventricular remodeling parameters [left ventricular end-diastolic diameter（LVEDD），left ventricular posterior wall thickness（LVPWT），interventricular septum thickness（IVST）] were determined，and left ventricular mass index（LVMI） was calculated. According to New York Heart Association（NYHA） classification，the CHF group was classified into Grade Ⅱ group（65 cases），Grade Ⅲ group（82 cases） and Grade Ⅳ group（48 cases）. Pearson correlation analysis was used to evaluate the correlation among the indicators. Logisitc regression analysis was used to evaluate the risk factors for poor prognosis in CHF patients. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of each indicator in determining poor prognosis in patients with CHF. Results Serum Cat-K and ADAMTS-7 in CHF group were higher than those in control group（P<0.05）. Serum Cat-K，ADAMTS-7，BNP，NT-proBNP，LVEDD，LVPWT，IVST and LVMI in NYHA Grade Ⅳ group were higher than those in NYHA Grade Ⅲ group and NYHA Grade Ⅱ group（P<0.05）. LVEF was lower than those of NYHA Grade Ⅲ group and NYHA Grade Ⅱ group（P<0.05）. Pearson correlation analysis showed that Cat-K and ADAMTS-7 were positively correlated with BNP，NT-proBNP，LVEDD，LVPWT，IVST and LVMI（P<0.05），and they were negatively correlated with LVEF（P<0.05）. Logistic regression analysis showed that the increasing of NT-proBNP，NYHA grade，Cat-K and ADAMTS-7 and the decreasing of LVEF were risk factors for poor prognosis in CHF patients [odds ratio（OR）=1.057，1.772，1.075，1.335 and 0.903，95% confidence intervals（CI） were 1.003-1.113，1.159-2.709，1.034-1.116，1.091-1.634 and 0.819-0.996，respectively]. The area under curve （AUC） of NT-proBNP，LVEF，NYHA grade，Cat-K and ADAMTS-7 in determining poor prognosis of CHF patients were 0.729，0.704，0.803，0.720，0.688 and 0.886，respectively. Conclusions Serum Cat-K and ADAMTS-7 are correlated with ventricular remodeling and poor prognosis in CHF patients.

Key words: Cathepsin K, A disintegrin and metalloproteinase with thrombospondin motifs 7, Ventricular remodeling, Chronic heart failure, Prognosis

CLC Number:

R446.1

LIANG Weizhang, SHI Jianping, CHAI Lina, HAN Aizi. Relationship between serum cathepsin K and ADAMTS-7 with ventricular remodeling and prognosis in patients with chronic heart failure[J]. Laboratory Medicine, 2023, 38(10): 919-925.

Figures/Tables 7

References 18

[1]	刘海燕, 宋毓青, 陈永福, 等. 沙库巴曲缬沙坦对射血分数降低型慢性心力衰竭患者的临床疗效及对B型脑钠肽和C反应蛋白水平的影响[J]. 中国医药, 2022, 17(1):15-18.
[2]	QIN L, LIU X, LI Y. Correlation of serum BNP and ET-1 levels with cardiac pump function and ventricular remodeling in patients with heart failure[J]. Cell Mol Biol(Noisy-le-grand), 2020, 66(3):125-131.
[3]	ZHANG X, LUO S, WANG M, et al. Cysteinyl cathepsins in cardiovascular diseases[J]. Biochim Biophys Acta Proteins Proteom, 2020, 1868(4):140360. DOI URL
[4]	WU W, ZHOU Y, LI Y, et al. Association between plasma ADAMTS-7 levels and ventricular remodeling in patients with acute myocardial infarction[J]. Eur J Med Res, 2015, 20(1):27. DOI URL
[5]	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.
[6]	BREDY C, MINISTERI M, KEMPNY A, et al. New York Heart Association(NYHA) classification in adults with congenital heart disease:relation to objective measures of exercise and outcome[J]. Eur Heart J Qual Care Clin Outcomes, 2018, 4(1):51-58. DOI URL
[7]	刘豪, 高毅娜, 关玲霞. 血清微小核糖核酸-30a及结缔组织生长因子对慢性心力衰竭患者心室重构及预后的关系[J]. 心肺血管病杂志, 2021, 40(5):410-415.
[8]	孙浩荣, 魏明慧, 范晓梅, 等. COX抑制剂对压力超负荷性心肌肥厚大鼠心室重构的作用[J]. 医学研究杂志, 2022, 51(7):85-91.
[9]	BARALLOBRE-BARREIRO J, RADOVITS T, FAVA M, et al. Extracellular matrix in heart failure:role of ADAMTS5 in proteoglycan remodeling[J]. Circulation, 2021, 144(25):2021-2034. DOI URL
[10]	HOES M F, TROMP J, OUWERKERK W, et al. The role of cathepsin D in the pathophysiology of heart failure and its potentially beneficial properties:a translational approach[J]. Eur J Heart Fail, 2020, 22(11):2102-2111. DOI URL
[11]	HUA Y, XU X, SHI G, et al. Cathepsin K knockout alleviates pressure overload-induced cardiac hypertrophy[J]. Hypertension, 2013, 61(6):1184-1192. DOI PMID
[12]	HUA Y, ROBINSON T J, CAO Y, et al. Cathepsin K knockout alleviates aging-induced cardiac dysfunction[J]. Aging Cell, 2015, 14(3):345-351. DOI PMID
[13]	HUA Y, ZHANG Y, DOLENCE J, et al. Cathepsin K knockout mitigates high-fat diet-induced cardiac hypertrophy and contractile dysfunction[J]. Diabetes, 2013, 62(2):498-509. DOI PMID
[14]	REN W, LIANG L, LI Y, et al. Upregulation of miR-423 improves autologous vein graft restenosis via targeting ADAMTS-7[J]. Int J Mol Med, 2020, 45(2):532-542.
[15]	COLIGE A, MONSEUR C, CRAWLEY J T B, et al. Proteomic discovery of substrates of the cardiovascular protease ADAMTS7[J]. J Biol Chem, 2019, 294(20):8037-8045. DOI PMID
[16]	SCHULZ J N, NÜCHEL J, NIEHOFF A, et al. COMP-assisted collagen secretion-a novel intracellular function required for fibrosis[J]. J Cell Sci, 2016, 129(4):706-716.
[17]	HUANG Y, XIA J, ZHENG J, et al. Deficiency of cartilage oligomeric matrix protein causes dilated cardiomyopathy[J]. Basic Res Cardiol, 2013, 108(5):374. DOI PMID
[18]	PÉREZ-GARCÍA S, CARRIÓN M, GUTIÉRREZ-CAÑAS I, et al. VIP and CRF reduce ADAMTS expression and function in osteoarthritis synovial fibroblasts[J]. J Cell Mol Med, 2016, 20(4):678-687. DOI URL

组别	例数	BMI/（kg/m²）	吸烟史/ [例（%）]	饮酒史/ [例（%）]	基础疾病史
组别	例数	BMI/（kg/m²）	吸烟史/ [例（%）]	饮酒史/ [例（%）]	糖尿病/[例（%）]	高脂血症/[例（%）]
CHF组	195	24.43±1.63	69（35.38）	79（40.51）	93（47.69）	65（33.33）
对照组	101	24.31±1.59	18（17.82）	22（21.78）	20（19.80）	14（13.86）
统计值		0.606	9.889	10.385	21.929	12.894
P值		0.545	0.002	<0.001	<0.001	<0.001

组别	例数	BMI/（kg/m²）	吸烟史/ [例（%）]	饮酒史/ [例（%）]	基础疾病史
组别	例数	BMI/（kg/m²）	吸烟史/ [例（%）]	饮酒史/ [例（%）]	糖尿病/[例（%）]	高脂血症/[例（%）]
CHF组	195	24.43±1.63	69（35.38）	79（40.51）	93（47.69）	65（33.33）
对照组	101	24.31±1.59	18（17.82）	22（21.78）	20（19.80）	14（13.86）
统计值		0.606	9.889	10.385	21.929	12.894
P值		0.545	0.002	<0.001	<0.001	<0.001

组别	例数	Cat-K/（pg/mL）	ADAMTS-7/（ng/mL）
CHF组	195	51.43±8.19	5.03±1.42
对照组	101	21.05±6.43	1.63±0.51
t值		35.002	29.917
P值		<0.001	<0.001

组别	例数	Cat-K/（pg/mL）	ADAMTS-7/（ng/mL）
CHF组	195	51.43±8.19	5.03±1.42
对照组	101	21.05±6.43	1.63±0.51
t值		35.002	29.917
P值		<0.001	<0.001

组别	例数	Cat-K/（pg/mL）	ADAMTS-7/（ng/mL）	BNP/（ng/L）	NT-proBNP/（ng/L）
NYHA Ⅱ级组	65	46.12±1.06	4.05±0.25	60.24±2.11	180.21±9.02
NYHA Ⅲ级组	82	52.05±3.68^*	5.13±1.06^*	72.12±6.47^*	201.26±15.02^*
NYHA Ⅳ级组	48	57.56±1.93^*#	6.19±0.27^*#	76.95±2.61^*#	234.44±3.06^*#
差异检验
F值		259.991	126.067	211.357	324.414
P值		<0.001	<0.001	<0.001	<0.001
趋势分析
χ²值		113.415	112.533	114.328	111.938
P值		<0.001	<0.001	<0.001	<0.001
组别	LVEDD/cm	LVPWT/mm	IVST/mm	LVMI/（g/m²）	LVEF/%
NYHA Ⅱ级组	50.52±0.31	9.02±0.41	9.32±0.47	118.52±2.15	60.22±2.28
NYHA Ⅲ级组	56.12±2.69^*	10.03±0.68^*	10.56±1.34^*	130.42±8.49^*	58.12±4.51^*
NYHA Ⅳ级组	60.45±0.51^*#	11.39±0.06^*#	12.06±0.41^*#	138.12±1.09^*#	51.72±0.85^*#
差异检验
F值	448.266	305.866	116.988	177.416	100.506
P值	<0.001	<0.001	<0.001	<0.001	<0.001
趋势分析
χ²值	113.999	112.372	113.158	114.682	89.223
P值	<0.001	<0.001	<0.001	<0.001	<0.001