Hennig B, Meerarani P, Ramadass P, Toborek M, Malecki A, Slim R, McClain C J
Department of Nutrition, University of Kentucky, Lexington 40506-0054, USA.
Nutrition. 1999 Oct;15(10):744-8. doi: 10.1016/s0899-9007(99)00148-3.
Little is known about the requirements and function of zinc in maintaining endothelial cell integrity, especially during stressful conditions, such as the inflammatory response in cardiovascular disease. There is evidence that zinc requirements of the vascular endothelium are increased during inflammatory conditions such as atherosclerosis, where apoptotic cell death is also prevalent. Apoptosis is a morphologically distinct mechanism of programmed cell death which involves the activation of a cell-intrinsic suicide program, and there is evidence that factors such as inflammatory cytokines (e.g., tumor necrosis factor [TNF]) and pure or oxidized lipids are necessary to induce the cell death pathway. Because of its constant exposure to blood components, including prooxidants, diet-derived fats, and their derivatives, the endothelium is very susceptible to oxidative stress and to apoptotic injury mediated by blood lipid components, prooxidants, and cytokines. Thus, it is likely that the cellular lipid environment, primarily polyunsaturated fatty acids, can potentiate the overall endothelial cell injury by increasing cellular oxidative stress and cytokine release in proximity to the endothelium, which then could further induce apoptosis and disrupt endothelial barrier function. Our data suggest that zinc deficiency exacerbates the detrimental effects of specific fatty acids (e.g., linoleic acid) and inflammatory cytokines, such as TNF, on vascular endothelial functions. We propose that a major mechanism of zinc protection against disruption of endothelial cell integrity during inflammatory conditions, is by the ability of zinc to inhibit the pathways of signal transduction leading to apoptosis and especially mechanisms that lead to upregulation of caspase genes.
关于锌在维持内皮细胞完整性方面的需求和功能，人们了解甚少，尤其是在应激状态下，如心血管疾病中的炎症反应期间。有证据表明，在诸如动脉粥样硬化等炎症状态下，血管内皮对锌的需求会增加，而在这些炎症状态下，细胞凋亡性死亡也很普遍。细胞凋亡是一种形态学上独特的程序性细胞死亡机制，涉及细胞内在自杀程序的激活，并且有证据表明，炎症细胞因子（如肿瘤坏死因子 [TNF]）以及纯脂质或氧化脂质等因素对于诱导细胞死亡途径是必要的。由于内皮细胞持续暴露于血液成分中，包括促氧化剂、饮食来源的脂肪及其衍生物，所以它极易受到氧化应激以及由血脂成分、促氧化剂和细胞因子介导的凋亡性损伤。因此，细胞脂质环境（主要是多不饱和脂肪酸）很可能通过增加细胞氧化应激以及在内皮细胞附近释放细胞因子来增强整体的内皮细胞损伤，进而可能进一步诱导细胞凋亡并破坏内皮屏障功能。我们的数据表明，锌缺乏会加剧特定脂肪酸（如亚油酸）和炎症细胞因子（如 TNF）对血管内皮功能的有害影响。我们提出，在炎症状态下，锌保护内皮细胞完整性免受破坏的主要机制是锌能够抑制导致细胞凋亡的信号转导途径，特别是导致半胱天冬酶基因上调的机制。
