Department of Geriatrics, Fujian Medical University Union Hospital, Fujian Key Laboratory of Vascular Aging (Fujian Medical University), Fujian Institute of Geriatrics, Department of Cardiology, Fujian Heart Disease Center, Fujian Clinical Research Center for Vascular and Brain Aging, Fuzhou, Fujian, 350001, China.
Adv Sci (Weinh). 2024 Apr;11(15):e2307040. doi: 10.1002/advs.202307040. Epub 2024 Feb 15.
Chronic inflammation is increasingly considered as the most important component of vascular aging, contributing to the progression of age-related cardiovascular diseases. To delay the process of vascular aging, anti-inflammation may be an effective measure. The anti-inflammatory factor annexin A1 (ANXA1) is shown to participate in several age-related diseases; however, its function during vascular aging remains unclear. Here, an ANXA1 knockout (ANXA1) and an endothelial cell-specific ANXA1 deletion mouse (ANXA1) model are used to investigate the role of ANXA1 in vascular aging. ANXA1 depletion exacerbates vascular remodeling and dysfunction while upregulates age- and inflammation-related protein expression. Conversely, Ac2-26 (a mimetic peptide of ANXA1) supplementation reverses this phenomenon. Furthermore, long-term tumor necrosis factor-alpha (TNF-α) induction of human umbilical vein endothelial cells (HUVECs) increases cell senescence. Finally, the senescence-associated secretory phenotype and senescence-related protein expression, rates of senescence-β-galactosidase positivity, cell cycle arrest, cell migration, and tube formation ability are observed in both ANXA1-knockdown HUVECs and overexpressed ANXA1-TNF-α induced senescent HUVECs. They also explore the impact of formyl peptide receptor 2 (a receptor of ANXA1) in an ANXA1 overexpression inflammatory model. These data provide compelling evidence that age-related inflammation in arteries contributes to senescent endothelial cells that promote vascular aging.
慢性炎症被认为是血管老化的最重要因素，它促进了与年龄相关的心血管疾病的进展。为了延缓血管老化的进程，抗炎可能是一种有效的措施。抗炎因子膜联蛋白 A1（ANXA1）被证明参与了几种与年龄相关的疾病；然而，其在血管老化过程中的作用尚不清楚。在这里，使用 ANXA1 敲除（ANXA1）和内皮细胞特异性 ANXA1 缺失（ANXA1）小鼠模型来研究 ANXA1 在血管老化中的作用。ANXA1 耗竭加剧了血管重构和功能障碍，同时上调了与年龄和炎症相关的蛋白表达。相反，Ac2-26（ANXA1 的模拟肽）的补充逆转了这种现象。此外，长期肿瘤坏死因子-α（TNF-α）诱导人脐静脉内皮细胞（HUVECs）增加细胞衰老。最后，在 ANXA1 敲低的 HUVECs 和过表达的 ANXA1-TNF-α诱导的衰老 HUVECs 中观察到衰老相关分泌表型和衰老相关蛋白表达、衰老-β-半乳糖苷酶阳性率、细胞周期停滞、细胞迁移和管形成能力的增加。他们还研究了在 ANXA1 过表达炎症模型中，甲酰肽受体 2（ANXA1 的受体）的影响。这些数据提供了令人信服的证据，表明动脉中的与年龄相关的炎症导致促进血管老化的衰老内皮细胞。
