Montreal Heart Institute, University of Montreal, Montreal, QC H1T 1C8, Canada.
Department of Pharmacology and Physiology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada.
Int J Mol Sci. 2021 Nov 12;22(22):12232. doi: 10.3390/ijms222212232.
Cellular senescence is a cell fate primarily induced by DNA damage, characterized by irreversible growth arrest in an attempt to stop the damage. Senescence is a cellular response to a stressor and is observed with aging, but also during wound healing and in embryogenic developmental processes. Senescent cells are metabolically active and secrete a multitude of molecules gathered in the senescence-associated secretory phenotype (SASP). The SASP includes inflammatory cytokines, chemokines, growth factors and metalloproteinases, with autocrine and paracrine activities. Among hundreds of molecules, angiopoietin-like 2 (angptl2) is an interesting, although understudied, SASP member identified in various types of senescent cells. Angptl2 is a circulatory protein, and plasma angptl2 levels increase with age and with various chronic inflammatory diseases such as cancer, atherosclerosis, diabetes, heart failure and a multitude of age-related diseases. In this review, we will examine in which context angptl2 was identified as a SASP factor, describe the experimental evidence showing that angptl2 is a marker of senescence in vitro and in vivo, and discuss the impact of angptl2-related senescence in both physiological and pathological conditions. Future work is needed to demonstrate whether the senescence marker angptl2 is a potential clinical biomarker of age-related diseases.
细胞衰老主要是由 DNA 损伤诱导的一种细胞命运，其特征是为了阻止损伤而发生不可逆的生长停滞。衰老作为细胞对压力源的反应，不仅发生在衰老过程中，也发生在伤口愈合和胚胎发育过程中。衰老细胞具有代谢活性，并分泌大量聚集在衰老相关分泌表型 (SASP) 中的分子。SASP 包括炎症细胞因子、趋化因子、生长因子和金属蛋白酶，具有自分泌和旁分泌活性。在数百种分子中，血管生成素样 2 (angptl2) 是一种有趣的、尽管研究较少的 SASP 成员，它存在于各种类型的衰老细胞中。Angptl2 是一种循环蛋白，其血浆水平随着年龄的增长以及各种慢性炎症性疾病（如癌症、动脉粥样硬化、糖尿病、心力衰竭和许多与年龄相关的疾病）而增加。在这篇综述中，我们将研究 angptl2 作为 SASP 因子的鉴定情况，描述表明 angptl2 是体外和体内衰老标志物的实验证据，并讨论与 angptl2 相关的衰老在生理和病理条件下的影响。需要进一步的研究来证明衰老标志物 angptl2 是否是与年龄相关的疾病的潜在临床生物标志物。
