Endothelial Senescence in Neurological Diseases

Xiao, Xuechun; Jiang, Huimin; Wei, Huimin; Zhou, Yifan; Ji, Xunming; Chen, Zhou

doi:10.14336/ad.2023.0226-1

Cited by 5 publications

(2 citation statements)

References 130 publications

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“…8 E). Cluster 3 showed high levels of EC markers such as TEK, CDH5, KDR, and PECAM1 but also exhibited elevated levels of EC senescent markers such as ESM1 [27,28], MMP1 and 2 [29], CDKN1a and 2a [30,28], IFGBP5 [31,32], IFI27, IFIT1, and PLAT [32]. These data suggest that cluster 3 mainly represents the senescent ECs (Fig.…”

Section: Resultsmentioning

confidence: 93%

A Single-Short Partial Reprogramming of the Endothelial Cells decreases Blood Pressure via attenuation of EndMT in Hypertensive Mice

Pernomian,

Waigi,

Nguyen

et al. 2024

Preprint

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Background: Small artery remodeling and endothelial dysfunction are hallmarks of hypertension. Growing evidence supports a likely causal association between cardiovascular diseases and the presence of endothelial-to-mesenchymal transition (EndMT), a cellular transdifferentiation process in which endothelial cells (ECs) partially lose their identity and acquire additional mesenchymal phenotypes. EC reprogramming represents an innovative strategy in regenerative medicine to prevent deleterious effects induced by cardiovascular diseases. Methods: Using a partial reprogramming of ECs, via overexpression of Oct-3/4, Sox-2, and Klf-4 (OSK) transcription factors, we aimed to bring ECs back to a youthful phenotype in hypertensive mice. Primary ECs were infected with lentiviral vectors (LV) containing the specific EC marker cadherin 5 (Cdh5) and the fluorescent reporter enhanced green fluorescence protein (EGFP) with empty vector (LVCO) or with OSK (LV-OSK). Confocal microscopy and western blotting analysis were used to confirm the OSK overexpression. Cellular migration, senescence, and apoptosis were evaluated. Human aortic ECs (HAoECs) from male and female normotensive and hypertensive patients were analyzed after OSK or control treatments for their endothelial nitric oxide synthase (eNOS) levels, nitric oxide (NO), and genetic profile. Male and female normotensive (BPN/3J) and hypertensive (BPH/2J) mice were treated with an intravenous (i.v.) injection of LVCO or LV-OSK and evaluated 10 days post-infection. The blood pressure, cardiac function, vascular reactivity of small arteries, in vivo EGFP signal and EndMT inhibition were analyzed. Results: OSK overexpression induced partial EC reprogramming in vitro, and these cells showed endothelial progenitor cell (EPC)-like features with lower migratory capability. OSK treatment of hypertensive BPH/2J mice normalized blood pressure and resistance arteries hypercontractility, via the attenuation of EndMT and elastin breaks. EGFP signal was detected in vivo in the prefrontal cortex of both BPN/3J and BPH/2J-treated mice, but OSK induced angiogenesis only in male BPN/3J mice. OSK-treated human ECs from hypertensive patients showed high eNOS activation and NO production, with low ROS formation. Single-cell RNA analysis showed that OSK alleviated EC senescence and EndMT, restoring their phenotypes in human ECs from hypertensive patients. Conclusion: Overall, these data indicate that OSK treatment and EC reprogramming can decrease blood pressure and reverse hypertension-induced vascular damage.

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Section: Resultsmentioning

confidence: 93%

A Single-Short Partial Reprogramming of the Endothelial Cells decreases Blood Pressure via attenuation of EndMT in Hypertensive Mice

Pernomian,

Waigi,

Nguyen

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Accumulation of senescent endothelial cells in the vascular bed results in increased expression of senescence-associated secretory phenotypes (SASPs), which also results in the senescence of adjacent cells in the vasculature. Eventually, vascular rarefaction and dysfunction occurs as risk factors and/or progression of many human diseases [162].…”

Section: Endothelial Senescence and Human Diseasesmentioning

confidence: 99%

Endothelial Senescence: From Macro- to Micro-Vasculature and Its Implications on Cardiovascular Health

Wang,

Konja,

Singh

et al. 2024

IJMS

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Endothelial cells line at the most inner layer of blood vessels. They act to control hemostasis, arterial tone/reactivity, wound healing, tissue oxygen, and nutrient supply. With age, endothelial cells become senescent, characterized by reduced regeneration capacity, inflammation, and abnormal secretory profile. Endothelial senescence represents one of the earliest features of arterial ageing and contributes to many age-related diseases. Compared to those in arteries and veins, endothelial cells of the microcirculation exhibit a greater extent of heterogeneity. Microcirculatory endothelial senescence leads to a declined capillary density, reduced angiogenic potentials, decreased blood flow, impaired barrier properties, and hypoperfusion in a tissue or organ-dependent manner. The heterogeneous phenotypes of microvascular endothelial cells in a particular vascular bed and across different tissues remain largely unknown. Accordingly, the mechanisms underlying macro- and micro-vascular endothelial senescence vary in different pathophysiological conditions, thus offering specific target(s) for therapeutic development of senolytic drugs.

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Non-pharmacological and drug treatment of autonomic dysfunction in multiple system atrophy: current status and future directions

et al. 2023

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Endothelial Senescence in Neurological Diseases

Cited by 5 publications

References 130 publications

A Single-Short Partial Reprogramming of the Endothelial Cells decreases Blood Pressure via attenuation of EndMT in Hypertensive Mice

A Single-Short Partial Reprogramming of the Endothelial Cells decreases Blood Pressure via attenuation of EndMT in Hypertensive Mice

Endothelial Senescence: From Macro- to Micro-Vasculature and Its Implications on Cardiovascular Health

Non-pharmacological and drug treatment of autonomic dysfunction in multiple system atrophy: current status and future directions

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