Toward Blood-Based Precision Medicine: Identifying Age-Sex-Specific Vascular Biomarker Quantities on Circulating Vascular Cells.

IF 2.3 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2023-07-06 eCollection Date: 2023-06-01 DOI:10.1007/s12195-023-00771-1

Yingye Fang, Ling Chen, P I Imoukhuede

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引用次数: 0

Abstract

Introduction: Abnormal angiogenesis is central to vascular disease and cancer, and noninvasive biomarkers of vascular origin are needed to evaluate patients and therapies. Vascular endothelial growth factor receptors (VEGFRs) are often dysregulated in these diseases, making them promising biomarkers, but the need for an invasive biopsy has limited biomarker research on VEGFRs. Here, we pioneer a blood biopsy approach to quantify VEGFR plasma membrane localization on two circulating vascular proxies: circulating endothelial cells (cECs) and circulating progenitor cells (cPCs).

Methods: Using quantitative flow cytometry, we examined VEGFR expression on cECs and cPCs in four age-sex groups: peri/premenopausal females (aged < 50 years), menopausal/postmenopausal females (≥ 50 years), and younger and older males with the same age cut-off (50 years).

Results: cECs in peri/premenopausal females consisted of two VEGFR populations: VEGFR-low (~ 55% of population: population medians ~ 3000 VEGFR1 and 3000 VEGFR2/cell) and VEGFR-high (~ 45%: 138,000 VEGFR1 and 39,000-236,000 VEGFR2/cell), while the menopausal/postmenopausal group only possessed the VEGFR-low cEC population; and 27% of cECs in males exhibited high plasma membrane VEGFR expression (206,000 VEGFR1 and 155,000 VEGFR2/cell). The absence of VEGFR-high cEC subpopulations in menopausal/postmenopausal females suggests that their high-VEGFR cECs are associated with menstruation and could be noninvasive proxies for studying the intersection of age-sex in angiogenesis. VEGFR1 plasma membrane localization in cPCs was detected only in menopausal/postmenopausal females, suggesting a menopause-specific regenerative mechanism.

Conclusions: Overall, our quantitative, noninvasive approach targeting cECs and cPCs has provided the first insights into how sex and age influence VEGFR plasma membrane localization in vascular cells.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-023-00771-1.

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迈向血液精准医学：识别循环血管细胞上年龄性别特异性血管生物标志物的数量。

简介：血管生成异常是血管疾病和癌症的核心，需要血管起源的无创生物标志物来评估患者和治疗。血管内皮生长因子受体（VEGFR）在这些疾病中经常失调，使其成为有前景的生物标志物，但对侵入性活检的需求限制了对VEGFR的生物标志性研究。在这里，我们开创了一种血液活检方法来量化VEGFR质膜在两种循环血管替代物上的定位：循环内皮细胞（cEC）和循环祖细胞（cPC）结果：绝经前后女性的cEC由两个VEGFR群体组成：VEGFR低(~ 55%的人口：人口中位数 ~ 3000 VEGFR1和3000 VEGFR2/细胞）和VEGFR高(~ 45%:138000 VEGFR1和39000-236000 VEGFR2/细胞），而绝经后/绝经后组仅具有VEGFR低cEC人群；雄性中27%的cEC表现出高质膜VEGFR表达（206000个VEGFR1和155000个VEGFR2/细胞）。绝经后/绝经后女性中缺乏VEGFR高cEC亚群，这表明她们的高VEGFR cEC与月经有关，可能是研究血管生成中年龄-性别交叉的非侵入性指标。VEGFR1在cPC中的质膜定位仅在绝经后/绝经后女性中检测到，这表明存在更年期特异性再生机制。结论：总体而言，我们针对cEC和cPC的定量、无创方法首次深入了解了性别和年龄如何影响血管细胞中VEGFR质膜的定位。补充信息：在线版本包含补充材料，请访问10.1007/s12195-023-00771-1。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.