Abstract

Aortic aneurysm, including thoracic aortic aneurysm and abdominal aortic aneurysm, is the second most prevalent aortic disease following atherosclerosis, representing the ninth‐leading cause of death globally. Open surgery and endovascular procedures are the major treatments for aortic aneurysm. Typically, thoracic aortic aneurysm has a more robust genetic background than abdominal aortic aneurysm. Abdominal aortic aneurysm shares many features with thoracic aortic aneurysm, including loss of vascular smooth muscle cells (VSMCs), extracellular matrix degradation and inflammation. Although there are limitations to perfectly recapitulating all features of human aortic aneurysm, experimental models provide valuable tools to understand the molecular mechanisms and test novel therapies before human clinical trials. Among the cell types involved in aortic aneurysm development, VSMC dysfunction correlates with loss of aortic wall structural integrity. Here, we discuss the role of VSMCs in aortic aneurysm development. The loss of VSMCs, VSMC phenotypic switching, secretion of inflammatory cytokines, increased matrix metalloproteinase activity, elevated reactive oxygen species, defective autophagy, and increased senescence contribute to aortic aneurysm development. Further studies on aortic aneurysm pathogenesis and elucidation of the underlying signaling pathways are necessary to identify more novel targets for treating this prevalent and clinical impactful disease.

中文翻译：

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主动脉瘤中的血管平滑肌细胞：从遗传学到机制

摘要

主动脉瘤，包括胸主动脉瘤和腹​​主动脉瘤，是仅次于动脉粥样硬化的第二大主动脉疾病，是全球第九大死因。开放手术和血管内手术是主动脉瘤的主要治疗方法。通常，胸主动脉瘤比腹主动脉瘤具有更强的遗传背景。腹主动脉瘤与胸主动脉瘤有许多共同特征，包括血管平滑肌细胞 (VSMC) 丢失、细胞外基质退化和炎症。尽管完美再现人类主动脉瘤的所有特征存在局限性，但实验模型提供了宝贵的工具，可以在人类临床试验之前了解分子机制和测试新疗法。在参与主动脉瘤发展的细胞类型中，VSMC 功能障碍与主动脉壁结构完整性的丧失相关。在这里，我们讨论了 VSMC 在主动脉瘤发展中的作用。VSMC 的损失、VSMC 表型转换、炎性细胞因子的分泌、基质金属蛋白酶活性增加、活性氧物质升高、自噬缺陷和衰老增加都有助于主动脉瘤的发展。有必要进一步研究主动脉瘤的发病机制和阐明潜在的信号通路，以确定更多新的靶点来治疗这种流行且具有临床影响的疾病。VSMC 表型转换、炎性细胞因子的分泌、基质金属蛋白酶活性增加、活性氧物质升高、自噬缺陷和衰老增加都有助于主动脉瘤的发展。有必要进一步研究主动脉瘤的发病机制和阐明潜在的信号通路，以确定更多新的靶点来治疗这种流行且具有临床影响的疾病。VSMC 表型转换、炎性细胞因子的分泌、基质金属蛋白酶活性增加、活性氧物质升高、自噬缺陷和衰老增加都有助于主动脉瘤的发展。有必要进一步研究主动脉瘤的发病机制和阐明潜在的信号通路，以确定更多新的靶点来治疗这种流行且具有临床影响的疾病。