Orlandi Augusto, Bochaton-Piallat Marie-Luce, Gabbiani Giulio, Spagnoli Luigi Giusto
Anatomic Pathology Institute, Department of Biopathology, Tor Vergata University of Rome, Via Montpellier 1, Rome, Italy.
Atherosclerosis. 2006 Oct;188(2):221-30. doi: 10.1016/j.atherosclerosis.2006.01.018. Epub 2006 Feb 17.
Epidemiological and autopsy studies suggest a close link between aging and the clinical manifestation of atherosclerosis. Several experiments show increased arterial susceptibility to atherogenetic stimuli in aged subjects. All together, these findings support the concept that aging represents an independent atherogenetic risk factor, intimately associated to other parietal, microenvironmental and systemic noxae. Smooth muscle cells (SMCs) represent the major arterial cell population. As aging occurs, SMCs progressively migrate from the tunica media and accumulate into the tunica intima. Myointimal thickening may represent the site where low-grade atherogenic stimuli cause early development and more severe lesion progression. Intimal SMC accumulation is characterized from a switch, from a differentiated to a synthetic phenotype, with reduced myocytic cytoskeletal markers and the expression of new proteins. Aging also associates to changes of SMC proliferative and apoptotic behavior and response to growth factors, such as transforming growth factor-beta1. The alteration of SMC properties represents a crucial event in the pathobiology of arterial wall, since it contributes to the vascular remodeling and decline of function with aging and favors the progression of atherosclerosis. Increased knowledge of biomolecular mechanisms regulating these events helps to develop new strategies aimed at contrasting the adverse effect of vascular aging.
流行病学和尸检研究表明，衰老与动脉粥样硬化的临床表现之间存在密切联系。多项实验表明，老年受试者的动脉对致动脉粥样硬化刺激的易感性增加。总体而言，这些发现支持了这样一种概念，即衰老代表一种独立的致动脉粥样硬化危险因素，与其他壁层、微环境和全身有害因素密切相关。平滑肌细胞（SMC）是动脉中的主要细胞群体。随着衰老的发生，SMC逐渐从血管中膜迁移并积聚到内膜。肌内膜增厚可能是低度致动脉粥样硬化刺激导致早期发展和更严重病变进展的部位。内膜SMC积聚的特征是从分化表型转变为合成表型，肌细胞细胞骨架标志物减少，新蛋白表达增加。衰老还与SMC增殖和凋亡行为的变化以及对生长因子（如转化生长因子-β1）的反应有关。SMC特性的改变是动脉壁病理生物学中的一个关键事件，因为它导致血管重塑和功能随衰老而下降，并促进动脉粥样硬化的进展。对调节这些事件的生物分子机制的更多了解有助于制定新的策略，以对抗血管衰老的不利影响。
