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

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Therapeutic Targets Pub Date : 2024-10-30 DOI:10.1080/14728222.2024.2421760
Wen Ma, Tingyuan Zhou, Songling Tang, Lu Gan, Yu Cao
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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.

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利用细胞外小泡靶向治疗心脑血管疾病中的衰老内皮细胞的利弊。
导言:随着人口老龄化的加剧,与年龄相关的疾病已成为全球的沉重负担,尤其是心脑血管疾病(CVDs)。内皮细胞(EC)衰老是心血管疾病发展的一个重要因素,这促使人们越来越关注缓解或逆转内皮细胞衰老的策略:细胞外小泡(sEVs)是细胞衍生的膜结构,含有蛋白质、脂类、RNA、代谢物、生长因子和细胞因子。它们被广泛用于治疗心血管疾病,并通过抑制或逆转心肌细胞衰老,在缓解与年龄相关的心血管疾病方面显示出显著的治疗潜力。然而,抗衰老机制的不明确给 sEVs 的临床应用带来了挑战,目前还缺乏系统的综述:专家观点:在与年龄相关的心血管疾病治疗中,用sEVs靶向衰老的心电子元件是一种很有前景的治疗策略,改变sEVs及其内容物正在成为一种流行的方法。然而,挑战依然存在,如识别和选择性靶向衰老细胞,了解去除衰老ECs和衰老相关分泌表型(SASP)的后果,以及评估治疗性sEVs对心血管疾病的副作用。推进临床实践需要更多的实验和临床数据。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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