Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics

Wang, Ding; Hao, Xinyu; Jia, Longyuan; Jing, Yuchen; Jiang, Bo; Xin, Shijie

doi:10.3389/fcvm.2022.999465

Cited by 4 publications

(4 citation statements)

References 158 publications

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“…Accordingly, mechanistic analyses of the cellular senescence and SASP development observed in the microenvironments of various diseases have been vigorously conducted in recent years [ 2 ]. Recent evidence shows that the onset and progression of age-related diseases, such as intervertebral disc degeneration (IDD) [ 5 , 6 , 7 ], osteoarthritis (OA) [ 8 , 9 , 10 , 11 ], and abdominal aortic aneurysm [ 12 , 13 , 14 ], are correlated with large numbers of senescent cells within the lesion.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Fujita,

Sasada,

Iyoda

et al. 2024

IJMS

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Senescence is a physiological and pathological cellular program triggered by various types of cellular stress. Senescent cells exhibit multiple characteristic changes. Among them, the characteristic flattened and enlarged morphology exhibited in senescent cells is observed regardless of the stimuli causing the senescence. Several studies have provided important insights into pro-adhesive properties of cellular senescence, suggesting that cell adhesion to the extracellular matrix (ECM), which is involved in characteristic morphological changes, may play pivotal roles in cellular senescence. Matricellular proteins, a group of structurally unrelated ECM molecules that are secreted into the extracellular environment, have the unique ability to control cell adhesion to the ECM by binding to cell adhesion receptors, including integrins. Recent reports have certified that matricellular proteins are closely involved in cellular senescence. Through this biological function, matricellular proteins are thought to play important roles in the pathogenesis of age-related diseases, including fibrosis, osteoarthritis, intervertebral disc degeneration, atherosclerosis, and cancer. This review outlines recent studies on the role of matricellular proteins in inducing cellular senescence. We highlight the role of integrin-mediated signaling in inducing cellular senescence and provide new therapeutic options for age-related diseases targeting matricellular proteins and integrins.

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Section: Introductionmentioning

confidence: 99%

Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Fujita,

Sasada,

Iyoda

et al. 2024

IJMS

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“…Growing evidence suggests that cellular senescence, a state of irreversible growth arrest, plays a crucial role in AAA development and progression. 15,16 Reactive oxygen species (ROS) have emerged as critical mediators of cellular senescence, with increased ROS levels being a hallmark of senescent cells. 17 Mitochondria and endoplasmic reticulum (ER) are both primary sources and targets of ROS generation, and the delicate balance between ROS production and detoxification is crucial for maintaining cellular homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…Aging‐related alterations in cellular processes and signaling pathways contribute to the pathogenesis of AAA. Growing evidence suggests that cellular senescence, a state of irreversible growth arrest, plays a crucial role in AAA development and progression 15,16 . Reactive oxygen species (ROS) have emerged as critical mediators of cellular senescence, with increased ROS levels being a hallmark of senescent cells 17 .…”

Section: Introductionmentioning

confidence: 99%

Higher matrix stiffness promotes VSMC senescence by affecting mitochondria–ER contact sites and mitochondria/ER dysfunction

He,

Zeng,

et al. 2023

The FASEB Journal

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Abdominal aortic aneurysm (AAA) is a prevalent condition characterized by the weakening and bulging of the abdominal aorta. This study aimed to investigate the impact of a stiff matrix on vascular smooth muscle cells (VSMCs) in AAA development. Bioinformatics analysis revealed that differentially expressed genes (DEGs) in VSMCs of an AAA mouse model were enriched in cellular senescence and related pathways. To simulate aging‐related changes, VSMCs were cultured on stiff matrices, and compared to those on soft matrices, the VSMCs cultured on stiff matrices exhibited cellular senescence. Furthermore, the mutual distance between mitochondria and endoplasmic reticulum (ER) in VSMCs was increased, indicating altered mitochondria–endoplasmic reticulum contacts (MERCs). The observed upregulation of reactive oxygen species (ROS) levels, antioxidant gene expression, and decreased mitochondrial membrane potential suggested the presence of mitochondrial dysfunction in VSMCs cultured on a stiff matrix. Additionally, the induction of ER stress‐related genes indicated ER dysfunction. These findings collectively indicated impaired functionality of both mitochondria and ER in VSMCs cultured on a stiff matrix. Moreover, our data revealed that high lipid levels exacerbated the effects of high matrix stiffness on VSMCs senescence, MERC sites, and mitochondria/ER dysfunction. Importantly, treatment with the antilipemic agent CI‐981 effectively reversed these detrimental effects. These findings provide insights into the role of matrix stiffness, mitochondrial dysfunction, ER stress, and lipid metabolism in AAA development, suggesting potential therapeutic targets for intervention.

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“…The pathological mechanism of AAA is complex, involving multiple biological processes that play important roles in its occurrence and development, mainly including oxidative stress, 8 chronic inflammation, 9 vascular senescence, 10 and cell death 11 . In recent years, the association between mitochondrial dysfunction and the pathogenesis of AAA has been gradually elaborated by many studies.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial quality control in abdominal aortic aneurysm: From molecular mechanisms to therapeutic strategies

et al. 2023

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Mitochondria are the energy supply sites of cells and are crucial for eukaryotic life. Mitochondrial dysfunction is involved in the pathogenesis of abdominal aortic aneurysm (AAA). Multiple mitochondrial quality control (MQC) mechanisms, including mitochondrial DNA repair, biogenesis, antioxidant defense, dynamics, and autophagy, play vital roles in maintaining mitochondrial homeostasis under physiological and pathological conditions. Abnormalities in these mechanisms may induce mitochondrial damage and dysfunction leading to cell death and tissue remodeling. Recently, many clues suggest that dysregulation of MQC is closely related to the pathogenesis of AAA. Therefore, specific interventions targeting MQC mechanisms to maintain and restore mitochondrial function have become promising therapeutic methods for the prevention and treatment of AAA.

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Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics

Cited by 4 publications

References 158 publications

Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Higher matrix stiffness promotes VSMC senescence by affecting mitochondria–ER contact sites and mitochondria/ER dysfunction

Mitochondrial quality control in abdominal aortic aneurysm: From molecular mechanisms to therapeutic strategies

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