Icosapent ethyl modulates circulating vascular regenerative cell content: The IPE-PREVENTION CardioLink-14 trial.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2024-07-12 Epub Date: 2024-03-28 DOI:10.1016/j.medj.2024.03.009

Ehab Bakbak, Aishwarya Krishnaraj, Deepak L Bhatt, Adrian Quan, Brady Park, Asaad I Bakbak, Basel Bari, Kristin A Terenzi, Yi Pan, Elizabeth J Fry, Daniella C Terenzi, Pankaj Puar, Tayyab S Khan, Ori D Rotstein, C David Mazer, Lawrence A Leiter, Hwee Teoh, David A Hess, Subodh Verma

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引用次数: 0

Abstract

Background: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) showed that icosapent ethyl (IPE) reduced major adverse cardiovascular events by 25%. Since the underlying mechanisms for these benefits are not fully understood, the IPE-PREVENTION CardioLink-14 trial (ClinicalTrials.gov: NCT04562467) sought to determine if IPE regulates vascular regenerative (VR) cell content in people with mild to moderate hypertriglyceridemia.

Methods: Seventy statin-treated individuals with triglycerides ≥1.50 and <5.6 mmol/L and either atherosclerotic cardiovascular disease or type 2 diabetes with additional cardiovascular risk factors were randomized to IPE (4 g/day) or usual care. VR cells with high aldehyde dehydrogenase activity (ALDH^hi) were isolated from blood collected at the baseline and 3-month visits and characterized with lineage-specific cell surface markers. The primary endpoint was the change in frequency of pro-vascular ALDH^hiside scatter (SSC)^lowCD133⁺ progenitor cells. Change in frequencies of ALDH^hiSSC^mid monocyte and ALDH^hiSSC^hi granulocyte precursor subsets, reactive oxygen species production, serum biomarkers, and omega-3 levels were also evaluated.

Findings: Baseline characteristics, cardiovascular risk factors, and medications were balanced between the groups. Compared to usual care, IPE increased the mean frequency of ALDH^hiSSC^lowCD133⁺ cells (-1.00% ± 2.45% vs. +7.79% ± 1.70%; p = 0.02), despite decreasing overall ALDH^hiSSC^low cell frequency. IPE assignment also reduced oxidative stress in ALDH^hiSSC^low progenitors and increased ALDH^hiSSC^hi granulocyte precursor cell content.

Conclusions: IPE-PREVENTION CardioLink-14 provides the first translational evidence that IPE can modulate VR cell content and suggests a novel mechanism that may underlie the cardioprotective effects observed with IPE in REDUCE-IT.

Funding: HLS Therapeutics provided the IPE in kind and had no role in the study design, conduct, analyses, or interpretation.

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伊可新戊酯可调节循环血管再生细胞的含量：IPE-PREVENTION CardioLink-14 试验。

背景：REDUCE-IT（伊可沙本乙酯减少心血管事件干预试验）显示，伊可沙本乙酯（IPE）可将主要不良心血管事件减少 25%。由于这些益处的潜在机制尚不完全清楚，IPE-PREVENTION CardioLink-14 试验（ClinicalTrials.gov：NCT04562467）试图确定 IPE 是否能调节轻度至中度高甘油三酯血症患者的血管再生（VR）细胞含量：从基线和3个月访视时采集的血液中分离出70名经他汀类药物治疗且甘油三酯≥1.50和hi）的患者，并用细胞系特异性细胞表面标记物进行表征。主要终点是促血管ALDHhiside散射（SSC）低CD133+祖细胞频率的变化。此外，还评估了ALDHhiSSCmid单核细胞和ALDHhiSSChi粒细胞前体亚群频率的变化、活性氧的产生、血清生物标志物和ω-3水平：研究结果：各组的基线特征、心血管风险因素和用药情况均衡。与常规护理相比，IPE增加了ALDHhiSSClowCD133+细胞的平均频率（-1.00% ± 2.45% vs. +7.79% ± 1.70%；p = 0.02），尽管降低了ALDHhiSSClow细胞的总体频率。IPE任务还降低了ALDHhiSSClow祖细胞的氧化应激，增加了ALDHhiSSChi粒细胞前体细胞的含量：IPE-PREVENTION CardioLink-14首次提供了IPE可调节VR细胞含量的转化证据，并提出了一种新的机制，可能是IPE在REDUCE-IT中观察到的心脏保护作用的基础：HLS Therapeutics以实物形式提供了IPE，但未参与研究的设计、实施、分析或解释。

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

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

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