背景:REDUCE-IT(使用Icosapent乙基干预试验减少心血管事件)显示,二十碳素乙基(IPE)可将主要不良心血管事件减少25%。由于这些好处的潜在机制尚未完全理解,IPE预防CardioLink-14试验(ClinicalTrials.gov:NCT04562467)旨在确定IPE是否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.
方法:将70名用他汀类药物治疗的甘油三酯≥1.50和<5.6mmol/L、动脉粥样硬化性心血管疾病或有其他心血管危险因素的2型糖尿病患者随机分配至IPE(4g/天)或常规治疗。从基线和3个月就诊时收集的血液中分离具有高醛脱氢酶活性(ALDHhi)的VR细胞,并用谱系特异性细胞表面标记物表征。主要终点是前血管ALDHhiside散射(SSC)低CD133+祖细胞频率的变化。ALDHhiSSCmid单核细胞和ALDHhiSSChi粒细胞前体亚群的频率变化,活性氧的产生,血清生物标志物,和ω-3水平也进行了评估。
结果:基线特征,心血管危险因素,两组之间的药物平衡。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),尽管总体ALDHhissc降低了细胞频率。IPE分配还降低了ALDHhiSSChi祖细胞的氧化应激,并增加了ALDHhiSSChi粒细胞前体细胞含量。
结论:IPE预防CardioLink-14提供了IPE可以调节VR细胞含量的第一个翻译证据,并提出了一种新机制,可能是IPE在REDUCE-IT中观察到的心脏保护作用的基础。
背景:HLSTherapeutics以实物形式提供了IPE,在研究设计中没有作用,行为,分析,或解释。
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.
RESULTS: 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.
BACKGROUND: HLS Therapeutics provided the IPE in kind and had no role in the
study design, conduct, analyses, or interpretation.