Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece.
Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany; Department of Cardiology, Center of Internal Medicine, Goethe University Frankfurt, Frankfurt, Germany; German Center of Cardiovascular Research (Deutsches Zentrum für Herz-Kreislaufforschung; DZHK), Rhein-Main Partner Site, Frankfurt, Germany.
Exp Gerontol. 2018 Aug;109:16-30. doi: 10.1016/j.exger.2017.06.007. Epub 2017 Jun 15.
Epidemiological studies have shown that ageing is a major non-reversible risk factor for cardiovascular disease. Vascular ageing starts early in life and is characterized by a gradual change of vascular structure and function resulting in increased arterial stiffening. At the present review we discuss the role of the most important molecular pathways involved in vascular ageing, their association with arterial stiffening and possible novel therapeutic targets that may delay this otherwise irreversible degenerating process. Specifically, we discuss the role of oxidative stress, telomere shortening, and ubiquitin proteasome system in endothelial cell senescence and dysfunction in vascular inflammation and in arterial stiffening. Further, we summarize the most important molecular mechanisms regulating vascular ageing including sirtuin 1, telomerase, klotho, JunD, and amyloid beta 1-40 peptide.
流行病学研究表明,衰老(ageing)是心血管疾病的一个主要不可逆转的风险因素。血管衰老(vascular ageing)很早就开始了,其特征是血管结构和功能的逐渐变化,导致动脉僵硬度增加。在本次综述中,我们讨论了参与血管衰老的最重要的分子途径的作用,它们与动脉僵硬度的关系,以及可能延缓这一不可逆转的退行性过程的新的治疗靶点。具体来说,我们讨论了氧化应激(oxidative stress)、端粒缩短(telomere shortening)和泛素蛋白酶体系统(ubiquitin proteasome system)在血管炎症和动脉僵硬度中内皮细胞衰老(endothelial cell senescence)和功能障碍中的作用。此外,我们总结了调节血管衰老的最重要的分子机制,包括沉默调节蛋白 1(sirtuin 1)、端粒酶(telomerase)、klotho、JunD 和淀粉样β1-40 肽。