Endothelial cell senescence exacerbates pulmonary hypertension through Notch-mediated juxtacrine signaling

Ramadhiani, Risa; Ikeda, Koji; Miyagawa, Kazuya; Ryanto, Gusty Rizky Teguh; Tamada, Naoki; Suzuki, Yoko; Hirata, Ken‐ichi; Emoto, Noriaki

doi:10.1101/2021.02.02.429321

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…First, it analyzes all genes rather than differentially expressed genes; second, it is good at detecting modest changes in individual genes by enhancing signal-to-noise ratio [15]. Other studies have found that senescence facilitates in ammation and vascular remodeling in PH [48,49]. A recent study found that Elimination of senescent cells by suicide gene or ABT263 accelerated pulmonary hemodynamics and pulmonary remodeling, decreased PAECs in hypoxia-induces PH, hypoxia + Sugeninduced PH, MCT-induced PH, and mice overexpressing the serotonin transporter [50].…”

Section: Discussionmentioning

confidence: 99%

Differentially Expressed Genes and Pathways between Reversible and Irreversible Pulmonary Arterial Hypertension Associated with Congenital Heart Disease Investigated by Bioinformatics Analysis in Rat Model

Zeng,

Lan,

Liu

et al. 2023

Preprint

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Background Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is one of the common types of PAH. Although the treatments of PAH–CHD are greatly advanced, it is still characterized by a poor prognosis, especially in its irreversible stage. The molecular mechanism underpinning the transition from the reversible stage to the irreversible stage is not well established. Methods and results GSE149899 was downloaded from Gene Expression Omnibus database, which is a dataset harvested from rat PH model induced by monocrotaline together with aortocaval shunt ((control (n = 5), reversible (n = 12), irreversible (n = 6)). R software was used to determine 252, 445, and 880 differentially expressed genes (DEGs) between the control group and the reversible PAH-CHD, the control group and the irreversible PAH-CHD, the reversible and irreversible PAH-CHD, respectively. Furthermore, we analyzed the biological functions of these DEGs. We concluded that common DEGs between reversible and irreversible PAH-CHD mainly enriched in the cell cycle, the p53 signaling pathway. The unique DEGs of reversible PAH-CHD involved in cell cycle, base excision repair. DEGs exclusively found in irreversible PAH-CHD were associated with complement and coagulation cascades, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway. Additionally, The P53 signaling pathway, ferroptosis, PI3K-Akt signaling pathway, IL-17 signaling pathway, cell cycle, complement and coagulation cascades were up-regulated both in reversible and irreversible groups, but up-regulation of the PI3K-Akt signaling pathway, cell cycle were more pronounced in the reversible group, whereas ferroptosis and complement and coagulation cascades was more pronounced in the irreversible group. The TNF signaling pathway, cellular senescence, and the AGE-RAGE signaling pathway were exclusively up-regulated in the reversible group, while the renin-angiotensin system was up-regulated and the AMPK signaling pathway was down-regulated exclusively in the irreversible groups. Conclusions The distinguishing pathways and hub genes between reversible and irreversible PAH-CHD may be attributable to the loss of reversibility of PAH-CHD in the end stages, and may cast new light on future research.

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Section: Discussionmentioning

confidence: 99%

Differentially Expressed Genes and Pathways between Reversible and Irreversible Pulmonary Arterial Hypertension Associated with Congenital Heart Disease Investigated by Bioinformatics Analysis in Rat Model

Zeng,

Lan,

Liu

et al. 2023

Preprint

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“…However, the functional role of EC glutaminolysis is uncharted to date. Meaningful knowledge might be borrowed from vascular remodeling in pulmonary hypertension, another disease featuring EC senes-cence [311,312]. Bertero et al reported that ECM stiffening increases GLS1 expression and enhances glutaminolytic flux and proliferation in cultured pulmonary arterial ECs [28].…”

Section: Senolysis-therapeutic Targeting Of Senescent Ecs 231 Pharmac...mentioning

confidence: 99%

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

Bu,

Yuan,

Xie

et al. 2023

IJMS

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Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

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The Aging Microenvironment in Lung Fibrosis

Deinhardt‐Emmer

Saux

2022

Curr. Tissue Microenviron. Rep.

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Purpose of Review To highlight the changes in lungs associated with senescent cells and the microbiome that promote a pro-inflammatory milieu and render the aged lungs at risk for debilitating chronic diseases such as cancer, chronic obstructive pulmonary disease, or pulmonary fibrosis. Recent Findings Recent studies including “omics” analyses indicate cell type-specific effects of aging and confirm the importance of the inflammation in aged lungs. Summary Aging of the lungs is driven by molecular and cellular processes that lead to loss of function and increased risk for diseases. The well-described nine hallmarks of aging are present in the aged lungs. Senescent cells combined with changes in the microbiome create the pro-inflammatory environment previously characterized in aged lungs. The pathobiology of one of the most devastating age-related pulmonary diseases, idiopathic pulmonary fibrosis (IPF), underscores the importance of senescent cells in the aged lungs.

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Endothelial cell senescence exacerbates pulmonary hypertension through Notch-mediated juxtacrine signaling

Cited by 3 publications

References 47 publications

Differentially Expressed Genes and Pathways between Reversible and Irreversible Pulmonary Arterial Hypertension Associated with Congenital Heart Disease Investigated by Bioinformatics Analysis in Rat Model

Differentially Expressed Genes and Pathways between Reversible and Irreversible Pulmonary Arterial Hypertension Associated with Congenital Heart Disease Investigated by Bioinformatics Analysis in Rat Model

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

The Aging Microenvironment in Lung Fibrosis

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