The emerging role of cell senescence in atherosclerosis

Wu, Chang-Meng; Zheng, Lei; Wang, Qian; Hu, Yan‐Wei

doi:10.1515/cclm-2020-0601

Cited by 55 publications

(44 citation statements)

References 91 publications

(75 reference statements)

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“…Senescence has been linked to atherogenic properties in cells such as endothelial cells [ 28 ] and vascular smooth muscle cells [ 29 ]. Interestingly, senescent macrophages have been shown to promote atherosclerosis through impaired cholesterol efflux [ 30 , 31 ], which is in agreement with our previous report of decreased cholesterol efflux in macrophages derived from Apoe −/− Neil3 −/− mice [ 3 ]. In the current study, several markers of cellular senescence, such as Acadsb [ 32 ], Baz2a [ 33 ] and Csde1 [ 34 ] were upregulated in Apoe −/− Neil3 −/− cells as compared to Apoe −/− cells, suggesting a process of beginning or progressing senescence in these cells.…”

Section: Discussionsupporting

confidence: 91%

NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length

Karlsen

Olsen

Kong

et al. 2022

Biochemistry and Biophysics Reports

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Deficiency of NEIL3, a DNA repair enzyme, has significant impact on mouse physiology, including vascular biology and gut health, processes related to aging. Leukocyte telomere length (LTL) is suggested as a marker of biological aging, and shortened LTL is associated with increased risk of cardiovascular disease. NEIL3 has been shown to repair DNA damage in telomere regions in vitro . Herein, we explored the role of NEIL3 in telomere maintenance in vivo by studying bone marrow cells from atherosclerosis-prone NEIL3-deficient mice. We found shortened telomeres and decreased activity of the telomerase enzyme in bone marrow cells derived from Apoe −/− Neil3 −/− as compared to Apoe −/− mice. Furthermore, Apoe −/− Neil3 −/− mice had decreased leukocyte levels as compared to Apoe −/− mice, both in bone marrow and in peripheral blood. Finally, RNA sequencing of bone marrow cells from Apoe −/− Neil3 −/− and Apoe −/− mice revealed different expression levels of genes involved in cell cycle regulation, cellular senescence and telomere protection. This study points to NEIL3 as a telomere-protecting protein in murine bone marrow in vivo .

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Section: Discussionsupporting

confidence: 91%

NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length

Karlsen

Olsen

Kong

et al. 2022

Biochemistry and Biophysics Reports

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“…Young or middle-aged CKD patients show premature endothelial aging [ 33 , 40 ]. Endothelial senescence in CKD patients is the consequence of multiple mediators [ 41 ]. One of these factors may be related to the fact that the endothelium of CKD patients is constantly exposed to numerous uremic toxins, such as IS and PC, causing cellular stress and cell damage [ 1 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Passage Number-Induced Replicative Senescence Modulates the Endothelial Cell Response to Protein-Bound Uremic Toxins

Guerrero

Carmona

Jiménez

et al. 2021

Toxins

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Endothelial aging may be induced early in pathological situations. The uremic toxins indoxyl sulfate (IS) and p-cresol (PC) accumulate in the plasma of chronic kidney disease (CKD) patients, causing accelerated endothelial aging, increased cardiovascular events and mortality. However, the mechanisms by which uremic toxins exert their deleterious effects on endothelial aging are not yet fully known. Thus, the aim of the present study is to determine the effects of IS and PC on endothelial damage and early senescence in cultured human umbilical vein endothelial cells (HUVECs). Hence, we establish an in vitro model of endothelial damage mediated by different passages of HUVECs and stimulated with different concentrations of IS and PC to evaluate functional effects on the vascular endothelium. We observe that cell passage-induced senescence is associated with apoptosis, ROS production and decreased endothelial proliferative capacity. Similarly, we observe that IS and PC cause premature aging in a dose-dependent manner, altering HUVECs’ regenerative capacity, and decreasing their cell migration and potential to form vascular structures in vitro. In conclusion, IS and PC cause accelerated aging in HUVECs, thus contributing to endothelial dysfunction associated with CKD progression.

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“…MCP-1 contributes to the T-cells and monocyte recruitment to the injured site on the vascular wall. Human monocytes were showed to express less amount of MCP-1 under exposure to Angiotensin II receptor blockers [10]. Other inflammatory molecules, such as IL-6, TNF-a, and COX-2 can also be upregulated by Angiotensin II.…”

Section: Figurementioning

confidence: 98%

Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD

Poznyak

Bharadwaj

Prasad

et al. 2021

IJMS

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Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin–angiotensin–aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.

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The emerging role of cell senescence in atherosclerosis

Cited by 55 publications

References 91 publications

NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length

NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length

Passage Number-Induced Replicative Senescence Modulates the Endothelial Cell Response to Protein-Bound Uremic Toxins

Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD

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