Semaglutide promotes bone marrow-derived progenitor cell flux towards an anti-inflammatory and pro-regenerative profile in high-risk patients: the SEMA-VR CardioLink-15 trial.

Since the turnover of vascular regenerative (VR) stem and progenitor cells has been demonstrated to modulate vessel repair and atherothrombotic risk, this study aimed to determine the effect of the GLP-1RA semaglutide on the levels of circulating VR cells.

由于已经证明血管再生（VR）干细胞和祖细胞的周转能够调节血管修复和动脉粥样硬化血栓形成风险，本研究旨在确定GLP-1RA司美格鲁肽对循环中VR细胞水平的影响。

Methods

SEMA-VR CardioLink-15 was a randomized translational trial of usual care vs semaglutide for 6 months in 46 participants with either type 2 diabetes and/or obesity plus atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk factors.

SEMA-VR CardioLink-15 是一项随机转化试验，比较了46名2型糖尿病和/或肥胖伴有动脉粥样硬化心血管疾病（ASCVD）或ASCVD风险因素的患者，接受常规治疗与使用司美格鲁肽6个月的疗效。

Vascular regenerative cells were enumerated using multi-parametric flow cytometry for high aldehyde dehydrogenase activity (ALDHhi) and lineage-specific cell surface marker expression.

使用多参数流式细胞术对高醛脱氢酶活性（ALDHhi）和特定谱系细胞表面标志物表达的血管再生细胞进行了计数。

The primary endpoint was the 6-month change in VR cell content.

主要终点是6个月VR细胞含量的变化。

Results

Compared with usual care (n = 24), semaglutide (n = 22) led to a greater increase in the number of VR cells [high aldehyde dehydrogenase 1A1 activity and low side scatter (ALDHhiSSClow): +0.8% vs +34.8%; P = .036], pan-haematopoietic myeloid progenitors (ALDHhiSSClowCD45+: +2.8% vs +40.1%; P = .017), and endothelial precursors (ALDHhiSSClowCD34+ CD133+ CD45-: -2.3% vs +66.2%; P = .037) from baseline.

与常规护理(n=24)相比，semaglutide(n=22)导致从基线开始，VR细胞数量的增加更大[高醛脱氢酶1A1活性和低侧向散射(ALDHhiSSClow): +0.8% vs +34.8%; P = .036]，全血细胞髓系祖细胞(ALDHhiSSClowCD45+: +2.8% vs +40.1%; P = .017)，以及内皮祖细胞(ALDHhiSSClowCD34+ CD133+ CD45-: -2.3% vs +66.2%; P = .037)。

Semaglutide also decreased granulocyte precursors (ALDHhiSSChi: +0.3% vs -50.8%; P = .002), particularly those expressing the neutrophil activation marker CD66b and chemokine receptor CXCR2.

Semaglutide 还减少了粒细胞前体（ALDHhiSSChi: +0.3% 对比 -50.8%; P = .002），尤其是那些表达中性粒细胞活化标记物 CD66b 和趋化因子受体 CXCR2 的细胞。

Semaglutide down-regulated serum proteins over-represented in pro-inflammatory tumour necrosis factor and interleukin signalling pathways.

Semaglutide 下调了血清蛋白，这些蛋白在促炎的肿瘤坏死因子和白细胞介素信号通路中过度表达。

Conclusions

In people living with either type 2 diabetes or obesity plus ASCVD risk, semaglutide increased circulating VR cell content while reducing pro-inflammatory granulocyte precursors and cytokine production.

在患有2型糖尿病或肥胖合并动脉粥样硬化心血管疾病（ASCVD）风险的人群中，司美格鲁肽增加了循环血管再生细胞（VR细胞）的数量，同时减少了促炎性粒细胞前体和细胞因子的产生。

Collectively, these findings suggest that semaglutide may improve endogenous progenitor cell-mediated blood vessel repair processes.

综合这些发现，表明司美格鲁肽可能改善了内源性祖细胞介导的血管修复过程。