MiR-17-5p Mediates the Effects of ACE2-Enriched Endothelial Progenitor Cell-Derived Exosomes on Ameliorating Cerebral Ischemic Injury in Aged Mice

Pan, Qiong; Wang, Yan; Liu, Jinhua; Jin, Xiaojuan; Xiang, Zhi; Li, Suqing; Shi, Yumeng; Chen, Yanfang; Zhong, Wangtao; Ma, Xiaotang

doi:10.1007/s12035-023-03280-4

Cited by 8 publications

(8 citation statements)

References 48 publications

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“…Interventions can alter the expression levels and enhance the functions of miRNAs in EPC-EXOs. ACE-overexpressing EPC-EXOs (ACE-EPC-EXOs) inhibit cellular senescence, EC oxidative stress, apoptosis, and dysfunction, thereby improving brain neurovascular injury in elderly mice with ischemic stroke, through the activation of the miR-17-5p/PTEN/PI3K/Akt signaling pathway [ 103 ]. Additionally, ACE-EPCs-EXOs downregulate Nox2/ROS through miR-18a to alleviate H/R injury in senescent ECs [ 104 ].…”

Section: Contents Of Epc-evsmentioning

confidence: 99%

“…In summary, EPC-EXOs that overexpress ACE have shown to inhibit cellular senescence, oxidative stress, apoptosis, and dysfunction in ECs, while activating the miR-17-5p/PTEN/PI3K/Akt signaling pathway. This mechanism has led to the amelioration of cerebral neurovascular injury in aged ischemic stroke mice [ 103 ]. These findings suggest that proteins contained within ECs hold therapeutic promise for CVDs.…”

Section: Contents Of Epc-evsmentioning

confidence: 99%

“…This protection was evidenced by a reduction in reactive oxygen species (ROS), an elevation in nitric oxide (NO) levels, and a decrease in the rate of apoptosis [ 104 ]. Additionally, ACE2-overexpressing EPC-EXOs demonstrated efficacy in ameliorating ischemic stroke in aged mice by mitigating cellular senescence, endothelial oxidative stress, apoptosis, and dysfunction through activation of the miR-17-5p/PTEN/PI3K/Akt signaling pathway [ 103 ]. Furthermore, loading of miR-210 enhanced the protective effects of EPC-EXOs against hypoxia/reoxygenation-induced neuronal apoptosis, oxidative stress, and reduced viability [ 102 ].…”

Section: Role Of Epc-evsmentioning

confidence: 99%

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Endothelial progenitor cell-derived extracellular vesicles: the world of potential prospects for the treatment of cardiovascular diseases

Chen,

Lu,

et al. 2024

Cell Biosci

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Cardiovascular diseases (CVDs) have emerged as a predominant threat to human health, surpassing the incidence and mortality rates of neoplastic diseases. Extracellular vesicles (EVs) serve as vital mediators in intercellular communication and material exchange. Endothelial progenitor cells (EPCs), recognized as precursors of vascular endothelial cells (ECs), have garnered considerable attention in recent years due to the potential therapeutic value of their derived extracellular vesicles (EPC-EVs) in the context of CVDs. This comprehensive review systematically explores the origins, characteristics, and functions of EPCs, alongside the classification, properties, biogenesis, and extraction techniques of EVs, with particular emphasis on their protective roles in CVDs. Additionally, we delve into the essential bioactive components of EPC-EVs, including microRNAs, long non-coding RNAs, and proteins, analyzing their beneficial effects in promoting angiogenesis, anti-inflammatory and anti-oxidant activities, anti-fibrosis, anti-apoptosis, and myocardial regeneration. Furthermore, this review comprehensively investigates the therapeutic potential of EPC-EVs across various CVDs, encompassing acute myocardial infarction, myocardial ischemia–reperfusion injury, atherosclerosis, non-ischemic cardiomyopathies, and diabetic cardiovascular disease. Lastly, we summarize the potential challenges associated with the clinical application of EPC-EVs and outline future directions, aiming to offer a valuable resource for both theoretical insights and practical applications of EPC-EVs in managing CVDs.

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Section: Contents Of Epc-evsmentioning

confidence: 99%

Section: Contents Of Epc-evsmentioning

confidence: 99%

Section: Role Of Epc-evsmentioning

confidence: 99%

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Endothelial progenitor cell-derived extracellular vesicles: the world of potential prospects for the treatment of cardiovascular diseases

Chen,

Lu,

et al. 2024

Cell Biosci

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“…[ 13 ] MiR‐17‐5p has been recognized as a crucial mediator of many diseases through the optimization of cellular functions. [ 14 , 15 , 16 ] For example, miR‐17‐5p was found to have therapeutic effects for brain tissue damage, [ 17 ] and osteoarthritis. [ 18 ] Furthermore, overexpression of miR‐17‐5p was found to protect from high glucose (HG)‐induced endothelial cell injury.…”

Section: Introductionmentioning

confidence: 99%

MiR‐17‐5p‐engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21

Wei,

Su,

Meng

et al. 2024

Advanced Science

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Delayed wound healing is a major complication of diabetes, and is associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports on microRNA expression in small extracellular vesicles (sEVs), miR‐17‐5p‐engineered sEVs (sEVs17‐OE) and encapsulated them in gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment are fabricated. SEVs17‐OE are successfully fabricated with a 16‐fold increase in miR‐17‐5p expression. SEVs17‐OE inhibited senescence and promoted the proliferation, migration, and tube formation of high glucose‐induced human umbilical vein endothelial cells (HG‐HUVECs). Additionally, sEVs17‐OE also performs a promotive effect on high glucose‐induced human dermal fibroblasts (HG‐HDFs). Mechanism analysis showed the expressions of p21 and phosphatase and tensin homolog (PTEN), as the target genes of miR‐17‐5p, are downregulated significantly by sEVs17‐OE. Accordingly, the downstream genes and pathways of p21 and PTEN, are activated. Next, sEVs17‐OE are loaded in GelMA hydrogel to fabricate a novel bioactive wound dressing and to evaluate their effects on diabetic wound healing. Gel‐sEVs17‐OE effectively accelerated wound healing by promoting angiogenesis and collagen deposition. The cellular mechanism may be associated with local cell proliferation. Therefore, a novel bioactive wound dressing by loading sEVs17‐OE in GelMA hydrogel, offering an option for chronic wound management is successfully fabricated.

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“…Given their excellent biological characteristics, including biocompatibility, stability, low toxicity, low immunogenicity, and efficient exchange of molecular cargos, exosomes can be potentially applied for disease treatment ( Patel et al, 2021 ; Wan et al, 2022 ; Xie et al, 2022 ). Recent studies demonstrated that exosomes derived from berberine-pretreated astrocytes, bone marrow-derived mesenchymal stem cells, endothelial progenitor cells, and neural stem cells can suppress neuroinflammation after stroke through different mechanisms ( Liu et al, 2021 ; Ding et al, 2023 ; Pan et al, 2023 ; Peng et al, 2023 ). Studies suggested that exosomes have protective effects on the brain by inhibiting inflammatory responses following ischemic stroke and have broad application prospects.…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression

Qin,

Zhou,

et al. 2024

Front. Pharmacol.

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Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male rats and oxygen-glucose-deprivation/reoxygenation (OGD/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke in vivo. H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, and the transcription factor Krüppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I/R injury by enhancing KLF14 expression.

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MiR-17-5p Mediates the Effects of ACE2-Enriched Endothelial Progenitor Cell-Derived Exosomes on Ameliorating Cerebral Ischemic Injury in Aged Mice

Cited by 8 publications

References 48 publications

Endothelial progenitor cell-derived extracellular vesicles: the world of potential prospects for the treatment of cardiovascular diseases

Endothelial progenitor cell-derived extracellular vesicles: the world of potential prospects for the treatment of cardiovascular diseases

MiR‐17‐5p‐engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21

Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression

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