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

{"title":"Icosapent ethyl modulates circulating vascular regenerative cell content: The IPE-PREVENTION CardioLink-14 trial.","authors":"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","doi":"10.1016/j.medj.2024.03.009","DOIUrl":null,"url":null,"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 (ALDHhi) 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 ALDHhiside scatter (SSC)lowCD133+ progenitor cells. Change in frequencies of ALDHhiSSCmid monocyte and ALDHhiSSChi 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 ALDHhiSSClowCD133+ cells (-1.00% ± 2.45% vs. +7.79% ± 1.70%; p = 0.02), despite decreasing overall ALDHhiSSClow cell frequency. IPE assignment also reduced oxidative stress in ALDHhiSSClow progenitors and increased ALDHhiSSChi 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.","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"718-734.e4"},"PeriodicalIF":12.8000,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Med","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.medj.2024.03.009","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

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。

求助全文

约1分钟内获得全文去求助

来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.