DNA damage and repair on hematopoietic stem cells: impact of oxidative stress in renovascular hypertension.

IF 1.5 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE
Giselle S Meireles, Rafaela Aires, Larissa Z Côco, Edgar H Kampke, Maria Es Barroso, Elisardo C Vasquez, Thiago Mc Pereira, Silvana S Meyrelles, Bianca P Campagnaro
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引用次数: 1

Abstract

Background: This study investigated oxidative damage to bone marrow cells in the pathogenesis of renovascular hypertension (RH).

Methods: Male C57BL/6 J mice (10-week-old and ~23 g) were divided into two groups: Sham-operated and 2K1C, which has a stainless-steel clip placed around the left renal artery. After twenty-eight days, the animals were anesthetized for hemodynamic measurements and bone marrow cells isolation. The intracellular production of ROS, DNA damage, and DNA repair kinetics were evaluated.

Results: Our results show that RH increases HSCs ROS production and that the 2K1C group showed a significant reduction of HSCs in the G0/G1 phase, increased p53 expression, DNA fragmentation, low DNA repair capacity, and a higher percentage of apoptotic cells when compared with the Sham group.

Conclusions: Our data imply that RH can compromise the hematopoiesis by increased oxidative stress leading to impaired DNA repair activity. Furthermore, this study provides new insights into the influence of hypertension on bone marrow homeostasis. This study showed for the first time that RH leads to oxidative damage, including genotoxic, to bone marrow cells. Thus, these findings provide new insights into the consequences of RH on bone marrow cells.

造血干细胞的DNA损伤和修复:氧化应激对肾血管性高血压的影响。
背景:本研究探讨肾血管性高血压(RH)发生过程中骨髓细胞的氧化损伤。方法:雄性C57BL/ 6j小鼠(10周龄,~23 g)分为假手术组和2K1C组,2K1C组在左肾动脉周围放置不锈钢夹。28天后,麻醉动物进行血流动力学测量和骨髓细胞分离。评估细胞内ROS的产生、DNA损伤和DNA修复动力学。结果:我们的研究结果表明,RH增加了hsc ROS的产生,与Sham组相比,2K1C组在G0/G1期明显减少hsc, p53表达增加,DNA片段化,DNA修复能力降低,凋亡细胞百分比更高。结论:我们的数据表明RH可以通过增加氧化应激导致DNA修复活性受损来损害造血功能。此外,本研究为高血压对骨髓稳态的影响提供了新的见解。这项研究首次表明RH导致骨髓细胞氧化损伤,包括基因毒性。因此,这些发现为RH对骨髓细胞的影响提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.90
自引率
0.80%
发文量
66
审稿时长
6-12 weeks
期刊介绍: Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.
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