Chu Jin, Praticò Domenico
Department of Pharmacology School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Cardiovasc Psychiatry Neurol. 2009;2009:174657. doi: 10.1155/2009/174657. Epub 2009 Sep 1.
Epidemiological studies indicate age as a strong risk factor for developing cardiovascular and neurodegenerative diseases. During the aging process, changes in the expression of particular genes can influence the susceptibility to these diseases. 5-Lipoxygenase (5-LO) by oxidizing fatty acids forms leukotrienes, potent mediators of oxidative and inflammatory reactions, two key pathogenic events in both clinical settings. This enzyme is widely distributed in the cardiovascular as well as in the central nervous system, where its expression levels increase with age, suggesting that it may be involved in their diseases of aging. The central theme of this article is that during aging, 5-LO acts as biologic link between different stressors and the development of cardiovascular and neurodegenerative diseases. We hypothesize that the age-dependent upregulation of 5-LO represents a "priming" factor in the vasculature as well as in the brain, where a subsequent exposure to triggering stimuli (i.e., infections) leads to an abnormal chronic inflammatory reaction, and ultimately results in increased organ vulnerability and functional deficits.
流行病学研究表明，年龄是心血管疾病和神经退行性疾病发生的一个重要风险因素。在衰老过程中，特定基因表达的变化会影响对这些疾病的易感性。5-脂氧合酶（5-LO）通过氧化脂肪酸形成白三烯，白三烯是氧化和炎症反应的强效介质，这两个关键的致病过程在两种临床情况下都会出现。这种酶广泛分布于心血管系统和中枢神经系统，其表达水平随年龄增长而升高，这表明它可能与衰老相关疾病有关。本文的核心观点是，在衰老过程中，5-LO作为不同应激源与心血管疾病和神经退行性疾病发展之间的生物学联系。我们假设，5-LO随年龄增长的上调代表了血管系统和大脑中的一个“启动”因素，在那里，随后接触触发刺激（如感染）会导致异常的慢性炎症反应，并最终导致器官易损性增加和功能缺陷。
