Lakatta Edward G
Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute, Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
J Am Soc Hypertens. 2007 Sep-Oct;1(5):302-40. doi: 10.1016/j.jash.2007.05.001.
The structure and function of central arteries change throughout the lifetime of humans and animals. Since atherosclerosis and hypertension are prevalent in epidemic proportion among older persons, it is reasonable to hypothesize that specific mechanisms that underlie the arterial substrate that has been altered by an "aging process" are intimately linked to arterial diseases. Indeed, recent studies reveal a profile of arterial cell and matrix properties that emerges with advancing age within the grossly normal appearing aortic wall of both animals and humans. This profile is proinflammatory, and is manifested by intimal infiltration of fetal cells, increased production of angiotensin II (Ang II)-signaling pathway molecules, eg, matrix metalloproteases (MMPs), and monocyte chemoattractant protein (MCP-1), transforming growth factor B1 (TGF-beta1), enhanced activation of MMPs, TGF-beta, and NADPH oxidase, and reduced nitric oxide (NO) bioavailability. This profile is similar to that induced at younger ages in experimental animal models of hypertension or atherosclerosis. In humans, this proinflammatory state, which occurs in the absence of lipid deposition, appears to be attributable to aging, per se. Other well known human risk factors, eg, altered lipid metabolism, smoking, and lack of exercise, interact with this arterial substrate that is altered by aging and render the aging human artery fertile soil for facilitation of the initiation and progression of arterial diseases. Therapies to reduce or retard this age-associated proinflammatory state within the grossly appearing arterial wall central arteries, in addition to slowing arterial aging, per se, may have a substantial impact on the quintessential age-associated arterial diseases of our society.
在人类和动物的一生中，中央动脉的结构和功能都会发生变化。由于动脉粥样硬化和高血压在老年人中呈流行态势，因此可以合理推测，由“衰老过程”改变的动脉基质所潜在的特定机制与动脉疾病密切相关。事实上，最近的研究揭示了在动物和人类外观大体正常的主动脉壁内，随着年龄增长出现的动脉细胞和基质特性概况。这种概况具有促炎性质，表现为胎儿细胞的内膜浸润、血管紧张素II（Ang II）信号通路分子（如基质金属蛋白酶（MMPs）和单核细胞趋化蛋白（MCP-1）、转化生长因子β1（TGF-β1））的产生增加、MMPs、TGF-β和NADPH氧化酶的激活增强以及一氧化氮（NO）生物利用度降低。这种概况类似于在高血压或动脉粥样硬化实验动物模型中较年轻时所诱导的情况。在人类中，这种在没有脂质沉积情况下出现的促炎状态似乎归因于衰老本身。其他众所周知的人类风险因素，如脂质代谢改变、吸烟和缺乏运动，与这种因衰老而改变的动脉基质相互作用，使衰老的人类动脉成为促进动脉疾病发生和发展的沃土。除了减缓动脉本身的衰老外，在外观大体正常的动脉壁中央动脉内减少或延缓这种与年龄相关的促炎状态的疗法，可能会对我们社会中典型的与年龄相关的动脉疾病产生重大影响。
