Fraile-Martinez Oscar, De Leon-Oliva Diego, Boaru Diego Liviu, De Castro-Martinez Patricia, Garcia-Montero Cielo, Barrena-Blázquez Silvestra, García-García Joaquin, García-Honduvilla Natalio, Alvarez-Mon Melchor, Lopez-Gonzalez Laura, Diaz-Pedrero Raul, Guijarro Luis G, Ortega Miguel A
Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala deHenares, Spain.
Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain.
Front Genet. 2024 Feb 26;15:1345459. doi: 10.3389/fgene.2024.1345459. eCollection 2024.
Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.
血管疾病构成了重大的健康挑战，了解其潜在的分子机制对于推进治疗干预至关重要。细胞衰老作为衰老的一个标志，是一种以细胞周期停滞、衰老相关分泌表型、大分子损伤和代谢失调为特征的细胞状态。血管衰老已被证明在不同的血管疾病中起关键作用，如动脉粥样硬化、外周动脉疾病、高血压、中风、糖尿病、慢性静脉疾病和静脉溃疡。尽管细胞衰老于1961年首次被描述，但在理解驱动血管衰老及其后续炎症反应的表观遗传机制方面仍存在重大差距。通过全面分析，我们旨在通过探索导致血管衰老的表观遗传改变网络来阐明这些知识差距。此外，我们描述了由这些表观遗传修饰引发的后续炎症级联反应。最后，我们探讨了涉及血管衰老生物标志物的转化应用以及针对这一生物学过程的新兴衰老疗法领域。
