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基于小细胞外囊泡靶向衰老内皮细胞在心血管和脑血管疾病中的利弊

Advantages and disadvantages of targeting senescent endothelial cells in cardiovascular and cerebrovascular diseases based on small extracellular vesicles.

作者信息

Ma Wen, Zhou Tingyuan, Tang Songling, Gan Lu, Cao Yu

机构信息

Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, China.

Department of Emergency Medicine and Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Expert Opin Ther Targets. 2024 Nov;28(11):1001-1015. doi: 10.1080/14728222.2024.2421760. Epub 2024 Oct 30.

Abstract

INTRODUCTION

With the growth of the aging population, age-related diseases have become a heavy global burden, particularly cardiovascular and cerebrovascular diseases (CVDs). Endothelial cell (EC) senescence constitutes an essential factor in the development of CVDs, prompting increased focus on strategies to alleviate or reverse EC senescence.

AREAS COVERED

Small extracellular vesicles (sEVs) are cell-derived membrane structures, that contain proteins, lipids, RNAs, metabolites, growth factors and cytokines. They are widely used in treating CVDs, and show remarkable therapeutic potential in alleviating age-related CVDs by inhibiting or reversing EC senescence. However, unclear anti-senescence mechanism poses challenges for clinical application of sEVs, and a systematic review is lacking.

EXPERT OPINION

Targeting senescent ECs with sEVs in age-related CVDs treatment represents a promising therapeutic strategy, with modifying sEVs and their contents emerging as a prevalent approach. Nevertheless, challenges remain, such as identifying and selectively targeting senescent cells, understanding the consequences of removing senescent ECs and senescence-associated secretory phenotype (SASP), and assessing the side effects of therapeutic sEVs on CVDs. More substantial experimental and clinical data are needed to advance clinical practice.

摘要

引言

随着老龄化人口的增长,与年龄相关的疾病已成为沉重的全球负担,尤其是心血管和脑血管疾病(CVD)。内皮细胞(EC)衰老构成了CVD发展的一个重要因素,促使人们更加关注缓解或逆转EC衰老的策略。

涵盖领域

小细胞外囊泡(sEV)是细胞衍生的膜结构,包含蛋白质、脂质、RNA、代谢物、生长因子和细胞因子。它们被广泛用于治疗CVD,并且在通过抑制或逆转EC衰老来缓解与年龄相关的CVD方面显示出显著的治疗潜力。然而,尚不明确的抗衰老机制给sEV的临床应用带来了挑战,并且缺乏系统的综述。

专家意见

在与年龄相关的CVD治疗中,用sEV靶向衰老的EC代表了一种有前景的治疗策略,修饰sEV及其内容物已成为一种普遍的方法。然而,挑战仍然存在,例如识别和选择性靶向衰老细胞、了解清除衰老EC和衰老相关分泌表型(SASP)的后果,以及评估治疗性sEV对CVD的副作用。需要更多实质性的实验和临床数据来推动临床实践。

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