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冠心病中前蛋白转化酶枯草溶菌素9、心脏动力学、氧化应激相互作用的研究:病例对照研究

Investigation of the interplay of PCSK9, cardiac dynamics, oxidative stress in coronary artery disease: case-control study.

作者信息

Lafta Anmar Hussein, Shiri Hamidreza, Iraji Mahsa, Karimpour Amin, Sattari Mahboobe, Rahimkhani Monireh, Einollahi Nahid, Panahi Ghodratollah

机构信息

Department of Clinical Laboratory Sciences, Faculty of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Front Endocrinol (Lausanne). 2025 Apr 28;16:1494438. doi: 10.3389/fendo.2025.1494438. eCollection 2025.

Abstract

BACKGROUND

PCSK9 plays a key role in raising LDL-C levels, which contributes to heart attacks (MI). However, studies show that about half of MI patients have normal LDL-C levels. This study aims to explore the link between PCSK9, heart function, and oxidative stress markers in MI patients.

METHODS

This investigation was carried out at Tehran Heart Centre Hospital on healthy individuals (n=63) and patients (n=63) with MI who had a coronary artery block above 50% (CAB > 50%). Oxidative stress (OS) parameters, such as total antioxidant capacity (TAC), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, PCSK9, oxidized Low-density lipoprotein (ox-LDL), high-sensitivity cardiac troponin I (hs-cTnI), and hs-CRP are assessed. Indeed, biochemical parameters and EF% were measured.

RESULTS

Higher EF% (>37.5%), TAC (>1.05 mmol Fe²;/L), GPx (>16.48 mU/mL), CAT (>11.32 nmol/min/mL), and SOD (>297.16 U/mL) were linked to a lower risk of CAB > 50%. In contrast, higher MDA (>32.07 nmol/mL), MPO (>17.77 U/L), hs-CRP (>5.5 mg/L), and ox-LDL (>64.87 μg/L) were associated with a higher risk. There was no significant difference in PCSK9 and LDL-C levels between groups. EF% was positively linked to SOD but negatively related to MDA, MPO, ox-LDL, hs-cTnI, and hs-CRP. Ox-LDL correlated positively with MPO but negatively with TAC, CAT, and GPx. PCSK9 showed a positive relationship with MDA. The best markers for CAB > 50% diagnosis were ox-LDL (AUC = 83.22, cut-off > 63.35 μg/L), EF% (AUC = 82.35, cut-off < 46.25%), and hs-cTnI (AUC = 81.3, cut-off > 0.265 ng/mL).

CONCLUSION

While PCSK9's role in MI through LDL-C is well known, its impact on inflammation and oxidative stress may also be important, even when LDL-C and PCSK9 levels are normal. Additionally, ox-LDL and EF% are better indicators of CAB > 50% than hs-cTnI.

摘要

背景

前蛋白转化酶枯草溶菌素9(PCSK9)在升高低密度脂蛋白胆固醇(LDL-C)水平方面起关键作用,而LDL-C水平升高会导致心脏病发作(心肌梗死,MI)。然而,研究表明,约一半的心肌梗死患者LDL-C水平正常。本研究旨在探讨心肌梗死患者中PCSK9、心脏功能和氧化应激标志物之间的联系。

方法

本调查在德黑兰心脏中心医院对健康个体(n = 63)和冠状动脉阻塞超过50%(CAB > 50%)的心肌梗死患者(n = 63)进行。评估氧化应激(OS)参数,如总抗氧化能力(TAC)、丙二醛(MDA)、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)活性、PCSK9、氧化型低密度脂蛋白(ox-LDL)、高敏心肌肌钙蛋白I(hs-cTnI)和超敏C反应蛋白(hs-CRP)。实际上,还测量了生化参数和射血分数(EF%)。

结果

较高的EF%(>37.5%)、TAC(>1.05 mmol Fe²⁺/L)、GPx(>16.48 mU/mL)、CAT(>11.32 nmol/min/mL)和SOD(>297.16 U/mL)与CAB > 50%的较低风险相关。相反,较高的MDA(>32.07 nmol/mL)、MPO(>17.77 U/L)、hs-CRP(>5.5 mg/L)和ox-LDL(>64.87 μg/L)与较高风险相关。各组之间PCSK9和LDL-C水平无显著差异。EF%与SOD呈正相关,但与MDA、MPO、ox-LDL、hs-cTnI和hs-CRP呈负相关。ox-LDL与MPO呈正相关,但与TAC、CAT和GPx呈负相关。PCSK9与MDA呈正相关。CAB > 50%诊断的最佳标志物是ox-LDL(曲线下面积[AUC] = 83.22,临界值>63.35 μg/L)、EF%(AUC = 82.35,临界值<46.25%)和hs-cTnI(AUC = 81.3,临界值>0.265 ng/mL)。

结论

虽然PCSK9通过LDL-C在心肌梗死中的作用已为人所知,但其对炎症和氧化应激的影响可能也很重要,即使LDL-C和PCSK9水平正常。此外,ox-LDL和EF%比hs-cTnI更能准确指示CAB > 50%。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34be/12066268/61a3754e6d0a/fendo-16-1494438-g001.jpg

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