Exogenous Hydrogen Sulfide Activates PI3K/Akt/eNOS Pathway to Improve Replicative Senescence in Human Umbilical Vein Endothelial Cells.

IF 1.8 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiology Research and Practice Pub Date : 2023-04-06 eCollection Date: 2023-01-01 DOI:10.1155/2023/7296874

Haiming Niu, Jianwei Li, Hongkai Liang, Guishen Wu, Miaolian Chen

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Abstract

Background: Endothelial cell senescence is one of the key mechanistic factors in the pathogenesis of atherosclerosis. In terms of molecules, the phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling plays an important role in the prevention and control of endothelial cell senescence, while hydrogen sulfide (H2S) improves the induced precocious senescence of endothelial cells through the PI3K/Akt/eNOS pathway. Comparatively, replicative senescence in endothelial cells is more in line with the actual physiological changes of human aging. This study aims to investigate the mechanism by which H2S improves endothelial cell replicative senescence and the involvement of the PI3K/Akt/eNOS pathway.

Methods: we established a model of replicative senescence in human umbilical vein endothelial cells (HUVECs) and explored the effect of 200 μmol/L sodium hydrosulfide (NaHS; a donor of H2S) on senescence, which was determined by cell morphology, the expression level of plasminogen activator inhibitor 1 (PAI-1), and the positive rate of senescence-associated β-galactosidase (SA-β-Gal) staining. Cell viability was detected by MTT assay to evaluate the effect of NaHS and the PI3K inhibitor, LY294002. Meanwhile, the protein expression of PI3K, Akt, p-Akt, and eNOS in endothelial cells of each group was detected by Western blot.

Results: the replicative senescence model was established in HUVECs at the passage of 16 cumulative cell population doubling values (CPDL). Treatment with NaHS not only significantly reduced the expression of PAI-1 and the positive rate of SA-β-Gal in HUVEC's replicative senescence model but also notably increased the expression of PI3K, p-Akt, p-eNOS, and the content of nitric oxide(NO). However, the effects of NaHS on the expression of the pathway and the content of NO in HUVECs were abolished when LY294002 specifically inhibited PI3K.

Conclusion: NaHS improves the replicative senescence of HUVECs with the contribution of the PI3K/Akt/eNOS pathway.

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外源硫化氢激活 PI3K/Akt/eNOS 通路，改善人脐静脉内皮细胞的复制衰老。

背景：内皮细胞衰老是动脉粥样硬化发病机理的关键因素之一。在分子方面，磷脂酰肌醇3-激酶/蛋白激酶B/内皮一氧化氮合酶（PI3K/Akt/eNOS）信号在预防和控制内皮细胞衰老中发挥着重要作用，而硫化氢（H2S）则通过PI3K/Akt/eNOS途径改善诱导的内皮细胞早衰。相对而言，内皮细胞的复制性衰老更符合人体衰老的实际生理变化。本研究旨在探讨 H2S 改善内皮细胞复制衰老的机制以及 PI3K/Akt/eNOS 通路的参与。方法：我们在人脐静脉内皮细胞（HUVECs）中建立了一个复制衰老模型，并探讨了 200 μmol/L 硫氢化钠（NaHS，H2S 的供体）对衰老的影响，衰老是通过细胞形态、纤溶酶原激活剂抑制剂 1（PAI-1）的表达水平和衰老相关的β-半乳糖苷酶（SA-β-Gal）染色阳性率来确定的。用 MTT 法检测细胞活力，以评估 NaHS 和 PI3K 抑制剂 LY294002 的效果。结果：HUVECs在16个累积细胞群倍增值（CPDL）时建立了复制衰老模型。NaHS不仅能明显降低HUVEC复制衰老模型中PAI-1的表达和SA-β-Gal的阳性率，还能显著增加PI3K、p-Akt、p-eNOS的表达和一氧化氮（NO）的含量。然而，当LY294002特异性抑制PI3K时，NaHS对HUVECs中PI3K、p-Akt、p-eNOS通路的表达和NO含量的影响被取消：结论：NaHS通过PI3K/Akt/eNOS通路改善了HUVECs的复制衰老。

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

Cardiology Research and Practice Medicine-Cardiology and Cardiovascular Medicine

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

13 weeks

期刊介绍： Cardiology Research and Practice is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies that focus on the diagnosis and treatment of cardiovascular disease. The journal welcomes submissions related to systemic hypertension, arrhythmia, congestive heart failure, valvular heart disease, vascular disease, congenital heart disease, and cardiomyopathy.