Ren Jie, Zhao Junhan, Yang Shengwen, An Shuoyan, Cai Chi, Wang Jing, Gu Min, Niu Hongxia, Li Shurong, Hua Wei, Gao Beiyao
Department of Cardiac Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
ESC Heart Fail. 2025 Jun;12(3):1640-1651. doi: 10.1002/ehf2.15175. Epub 2024 Dec 27.
Biomarkers are pivotal in the management of heart failure (HF); however, their lack of cardiac specificity could limit clinical utility. This study aimed to investigate the transcoronary changes and intracardiac production of these biomarkers.
Transcoronary gradients for B-type natriuretic peptide (BNP) and five novel biomarkers-galectin-3 (Gal-3), soluble suppression of tumourigenicity 2 (sST2), tissue inhibitor of metalloproteinase 1 (TIMP-1), growth differentiation factor 15 (GDF-15) and myeloperoxidase (MPO)-were determined using femoral artery (FA) and coronary sinus (CS) samples from 30 HF patients and 10 non-HF controls. Intracardiac biomarker production was assessed in an HF canine model using real-time quantitative PCR (qPCR) and western blot (WB) analysis.
Compared with the control group, levels of all detected biomarkers were significantly elevated in the HF group, while transcoronary gradients were only observed for BNP, Gal-3 and TIMP-1 levels in the HF group (BNP: FA: 841.5 ± 727.2 ng/mL vs. CS: 1132.0 ± 959.1 ng/mL, P = 0.005; Gal-3: FA: 9.5 ± 3.0 ng/mL vs. CS: 19.7 ± 16.4 ng/mL, P = 0.002; and TIMP-1: FA: 286.7 ± 68.9 ng/mL vs. CS: 377.3 ± 108.9 ng/mL, P = 0.001). Real-time qPCR and WB analysis revealed significant elevation of BNP, Gal-3 and TIMP-1 in the cardiac tissues of the HF group relative to other groups.
This study provided evidence of transcoronary changes in BNP, Gal-3 and TIMP-1 levels in HF patients, offering insights into their intracardiac production. These findings enhance the understanding of the biology of these biomarkers and may inform their clinical application.
生物标志物在心力衰竭(HF)的管理中起着关键作用;然而,它们缺乏心脏特异性可能会限制其临床应用。本研究旨在调查这些生物标志物的跨冠状动脉变化及心内生成情况。
使用来自30例HF患者和10例非HF对照的股动脉(FA)和冠状窦(CS)样本,测定B型利钠肽(BNP)以及五种新型生物标志物——半乳糖凝集素-3(Gal-3)、可溶性肿瘤抑制因子2(sST2)、金属蛋白酶组织抑制剂1(TIMP-1)、生长分化因子15(GDF-15)和髓过氧化物酶(MPO)的跨冠状动脉梯度。使用实时定量聚合酶链反应(qPCR)和蛋白质印迹(WB)分析,在HF犬模型中评估心内生物标志物的生成情况。
与对照组相比,HF组中所有检测到的生物标志物水平均显著升高,而HF组中仅观察到BNP、Gal-3和TIMP-1水平的跨冠状动脉梯度(BNP:FA:841.5±727.2 ng/mL vs. CS:1132.0±959.1 ng/mL,P = 0.005;Gal-3:FA:9.5±3.0 ng/mL vs. CS:19.7±16.4 ng/mL,P = 0.002;TIMP-1:FA:286.7±68.9 ng/mL vs. CS:377.3±108.9 ng/mL,P = 0.001)。实时qPCR和WB分析显示,相对于其他组,HF组心脏组织中BNP、Gal-3和TIMP-1显著升高。
本研究提供了HF患者中BNP、Gal-3和TIMP-1水平跨冠状动脉变化的证据,有助于深入了解它们的心内生成情况。这些发现加深了对这些生物标志物生物学特性的理解,并可能为其临床应用提供参考。