Pulmonary hypertension induced right heart failure via upregulation of serum Dickkopf-1 expression

IF 3.2 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

International journal of cardiology Pub Date : 2025-06-05 DOI:10.1016/j.ijcard.2025.133481

Ziqing Wang , Qianqian Wang , Hao Xu, Haojie Zhang, Shaojun Ren, Yimin Sun, Junhua Ge , Jian Li

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引用次数: 0

Abstract

Background

Pulmonary hypertension (PH)-induced right heart failure (RHF) is a progressive syndrome characterized by right ventricular (RV) enlargement and dysfunction. This study aimed to investigate factors associated with PH-induced RHF, with a focus on the role of Dickkopf-1 (DKK1).

Method

Clinical data and serum samples were collected from healthy controls (n = 18), patients with PH (n = 29), and PH-RHF (n = 75). DKK1 expression was quantified in serum and RV tissue.

Results

Serum DKK1 levels were significantly elevated in PH and PH-RHF patients compared to controls (1396.36 ± 413.40 vs. 2502.51 ± 962.81 vs. 3798.33 ± 1936.17 pg/mL, P < 0.001). Higher DKK1 levels were associated with impaired RV function, reflected by reduced TAPSE (P = 0.025), lower TAPSE/sPAP ratio (P = 0.024), and elevated sPAP (P = 0.017). DKK1 also correlated with invasive hemodynamic parameters, including RVP (P = 0.006), mPAP (P < 0.001), PVR (P = 0.014), SVR (P = 0.003), CO (P = 0.023), and CI (P = 0.002). Experimental models demonstrated marked DKK1 upregulation in hypoxia-stimulated cardiomyocytes and in serum and RV tissue of monocrotaline-treated and PAB rats.

Conclusions

Elevated DKK1 levels are associated with worsening RV dysfunction in PH, suggesting a potential pathogenic role in PH-induced RHF. DKK1 may serve as a complementary biomarker and a potential therapeutic target in PH-related RHF.

查看原文本刊更多论文

肺动脉高压通过上调血清Dickkopf-1表达诱发右心衰。

背景：肺动脉高压（pH）引起的右心衰（RHF）是一种以右心室（RV）扩大和功能障碍为特征的进行性综合征。本研究旨在探讨ph诱导RHF的相关因素，重点关注Dickkopf-1 （DKK1）的作用。方法：收集健康对照（n = 18）、PH患者（n = 29）和PH- rhf患者（n = 75）的临床资料和血清样本。测定血清和RV组织中DKK1的表达。结果：与对照组相比，PH和PH-RHF患者血清DKK1水平显著升高（1396.36 ± 413.40 vs. 2502.51 ± 962.81 vs. 3798.33 ± 1936.17 pg/mL, P ）结论：DKK1水平升高与PH下RV功能障碍恶化有关，提示在PH诱导的RHF中具有潜在的致病作用。DKK1可作为ph相关RHF的补充生物标志物和潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International journal of cardiology 医学-心血管系统

CiteScore

6.80

自引率

5.70%

发文量

758

审稿时长

44 days

期刊介绍： The International Journal of Cardiology is devoted to cardiology in the broadest sense. Both basic research and clinical papers can be submitted. The journal serves the interest of both practicing clinicians and researchers. In addition to original papers, we are launching a range of new manuscript types, including Consensus and Position Papers, Systematic Reviews, Meta-analyses, and Short communications. Case reports are no longer acceptable. Controversial techniques, issues on health policy and social medicine are discussed and serve as useful tools for encouraging debate.