Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging

Hwang, Han-Jeong; Kim, Nayeon; Herman, Allison N.; Gorospe, Myriam; Lee, Jae‐Seon

doi:10.3390/ijms231710135

Cited by 38 publications

(26 citation statements)

References 149 publications

(164 reference statements)

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“…Among these detrimental effects of senescent cell accumulation, complications in the cardiovascular system have been the subject of several recent studies. For example, senescent endothelial cells (ECs) exhibit functional abnormalities, such as decreased expression of endothelial nitric oxide (NO) synthase and increased expression of proinflammatory molecules, contributing to vascular inflammation [34][35][36]. Senescent ECs and other senescent cell types in the cardiovascular system share characteristics with other types of dysfunctional cells.…”

Section: Introductionmentioning

confidence: 99%

Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Suda

Paul

Minamino

et al. 2023

Cells

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Senescent cell accumulation has been observed in age-associated diseases including cardiovascular diseases. Senescent cells lack proliferative capacity and secrete senescence-associated secretory phenotype (SASP) factors that may cause or worsen many cardiovascular diseases. Therapies targeting senescent cells, especially senolytic drugs that selectively induce senescent cell removal, have been shown to delay, prevent, alleviate, or treat multiple age-associated diseases in preclinical models. Some senolytic clinical trials have already been completed or are underway for a number of diseases and geriatric syndromes. Understanding how cellular senescence affects the various cell types in the cardiovascular system, such as endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells, progenitor cells, and cardiomyocytes, is important to facilitate translation of senotherapeutics into clinical interventions. This review highlights: (1) the characteristics of senescent cells and their involvement in cardiovascular diseases, focusing on the aforementioned cardiovascular cell types, (2) evidence about senolytic drugs and other senotherapeutics, and (3) the future path and clinical potential of senotherapeutics for cardiovascular diseases.

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Section: Introductionmentioning

confidence: 99%

Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Suda

Paul

Minamino

et al. 2023

Cells

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“…High glucose conditions induce premature endothelial cell aging, leading to CBF dysregulation ( Biessels and Despa, 2018 ; Prattichizzo et al, 2018 ; Balasubramanian et al, 2021 ). A recent review ( Hwang et al, 2022 ) extensively summarized the molecular pathways related to endothelial cell aging. Understanding these diabetes-related changes in pathways is of significant importance for improving endothelial dysfunction and CBF dysregulation.…”

Section: Evidence Of Cognitive Decline In Diabetes Patientsmentioning

confidence: 99%

The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

Feng,

Gao

2024

Front. Neurosci.

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Neurovascular coupling (NVC) is an important mechanism to ensure adequate blood supply to active neurons in the brain. NVC damage can lead to chronic impairment of neuronal function. Diabetes is characterized by high blood sugar and is considered an important risk factor for cognitive impairment. In this review, we provide fMRI evidence of NVC damage in diabetic patients with cognitive decline. Combined with the exploration of the major mechanisms and signaling pathways of NVC, we discuss the effects of chronic hyperglycemia on the cellular structure of NVC signaling, including key receptors, ion channels, and intercellular connections. Studying these diabetes-related changes in cell structure will help us understand the underlying causes behind diabetes-induced NVC damage and early cognitive decline, ultimately helping to identify the most effective drug targets for treatment.

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“…Cell senescence is a state of indefinite cell cycle arrest implemented in response to sublethal stresses (Hwang et al, 2022). Current studies have found that dietary restriction (DR) without malnutrition is the most effective way to prevent cell senescence in humans, and in vivo experiments revealed that inhibition of mTORC1 activity in yeast, nematodes, flies, and mammals can lead to a longer lifespan (Vellai et al, 2003;Kapahi et al, 2004;Kaeberlein et al, 2005;Wu et al, 2013;Green et al, 2022).…”

Section: Mtor Signaling Pathway-mediated Cell Senescence In the Patho...mentioning

confidence: 99%

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review

Liu

et al. 2023

Front. Pharmacol.

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Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS.

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Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging

Cited by 38 publications

References 149 publications

Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review

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