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老年患者血管僵硬度与衰老细胞生物标志物之间的相关性

[Correlations between vessel stiffness and biomarkers of senescent cell in elderly patients].

作者信息

Sorokina A G, Efimenko A Yu, Grigorieva O A, Novoseletskaya E S, Basalova N A, Aleksandrushkina N A, Vigovskiy M A, Kirillova K I, Strazhesko I D, Orlov A V, Balatskiy A V, Samokhodskaya L М, Danilova N V, Dychkova U D, Akopyan A A, Kakotkin V V, Asratyan D A, Akopyan Z A, Orlova Ya A

机构信息

Medical Research and Educational Center, Lomonosov Moscow State University; Faculty of Fundamental Medicine, Lomonosov Moscow State University.

Medical Research and Educational Center, Lomonosov Moscow State University.

出版信息

Kardiologiia. 2022 Jun 30;62(6):15-22. doi: 10.18087/cardio.2022.6.n2033.

Abstract

Aim    To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods    This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated. Also, biomaterials (peripheral blood, skin, subcutaneous adipose tissue) were collected during the surgery and were used for isolation of several cell types and subsequent histological analysis to determine various markers of senescent cells.Results    The study included 80 patients aged 65 to 90 years. The correlation analysis identified the most significant indexes that reflected the accumulation of senescent cells at the systemic, tissue, and cellular levels (r>0.3, р<0.05) and showed positive and negative correlations with PWV. The following blood plasma factors were selected as the markers of ageing: insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF-21), and vascular endothelium adhesion molecule 1 (VCAM-1). A significant negative correlation between PWV and IGF-1 concentration was found. Among the tissue markers, P16INK, the key marker for tissue accumulation of senescent cells, predictably showed a positive correlation (r=0.394, p<0.05). A medium-strength correlation with parameters of the 96-h increment of mesenchymal stromal cells and fibroblasts and a weak correlation with IL-6 as a SASP (specific senescent-associated secretory phenotype) were noted. Results of the multifactorial linear regression analysis showed that the blood plasma marker, VCAM-1, and the cell marker, 96-h increment of fibroblasts, were associated with PWV regardless of the patient's age.Conclusion    Stiffness of great arteries as measured by PWV significantly correlates with a number of plasma, tissue, and cellular markers for accumulation of senescent cells. This fact suggests PWV as a candidate for inclusion in the panel of parameters for evaluation and monitoring of the biological age during the senolytic therapy.

摘要

目的 研究老年患者血管壁僵硬度与血液、细胞和组织中衰老细胞积累的已知标志物之间的关联。

材料与方法 本研究纳入了65岁及以上因择期手术前来就诊的男性和女性患者,手术包括在前腹壁或大关节区域进行手术切口,且符合纳入和排除标准。对所有患者评估传统心血管(CV)危险因素和动脉壁僵硬度(脉搏波速度,PWV)。此外,在手术过程中收集生物材料(外周血、皮肤、皮下脂肪组织),用于分离多种细胞类型并随后进行组织学分析,以确定衰老细胞的各种标志物。

结果 本研究纳入了80例年龄在65至90岁之间的患者。相关性分析确定了反映衰老细胞在全身、组织和细胞水平积累的最显著指标(r>0.3,p<0.05),并显示与PWV呈正相关和负相关。选择以下血浆因子作为衰老标志物:胰岛素样生长因子1(IGF-1)、成纤维细胞生长因子21(FGF-21)和血管内皮黏附分子1(VCAM-1)。发现PWV与IGF-1浓度之间存在显著负相关。在组织标志物中,衰老细胞组织积累的关键标志物P16INK可预见地显示出正相关(r = 0.394,p<0.05)。注意到与间充质基质细胞和成纤维细胞96小时增殖参数存在中等强度相关性,与作为衰老相关分泌表型(SASP)的白细胞介素-6存在弱相关性。多因素线性回归分析结果表明,无论患者年龄如何,血浆标志物VCAM-1和细胞标志物成纤维细胞96小时增殖均与PWV相关。

结论 通过PWV测量的大动脉僵硬度与衰老细胞积累的多种血浆、组织和细胞标志物显著相关。这一事实表明PWV可作为在衰老细胞溶解疗法期间评估和监测生物学年龄的参数面板中的候选指标。

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