Massaro Marika, Scoditti Egeria, Carluccio Maria Annunziata, Montinari Maria Rosa, De Caterina Raffaele
CNR Institutes of Clinical Physiology, Pisa and Lecce, Italy.
J Nutrigenet Nutrigenomics. 2008;1(1-2):4-23. doi: 10.1159/000109871. Epub 2007 Oct 17.
Atherosclerosis is a dynamic process with inflammatory aspects playing a considerable pathogenetic role. In this process, the vascular endothelium is the key regulator of vascular function, promoting the maintenance of vascular homeostasis or the progression towards vascular disease. In the past 30 years, the dietary intake of omega-3 (n-3) polyunsaturated fatty acids - mainly derived from fish - has emerged as an important way to modify cardiovascular risk through beneficial effects on all stages of atherosclerosis. This review specifically focuses on the modulating effects of n-3 fatty acids on molecular events involved in early and late atherogenesis, including effects on endothelial expression of adhesion molecules, as well as pro-inflammatory and pro-angiogenic enzymes. By accumulating in endothelial membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of several genes through a decreased activation of the nuclear factor-kappaB system of transcription factors. This occurs secondary to decreased generation of intracellular reactive oxygen species. This series of investigations configures a clear example of nutrigenomics, i.e. how nutrients may affect gene expression, ultimately affecting a wide spectrum of human diseases.
动脉粥样硬化是一个动态过程,炎症在其发病机制中起着相当重要的作用。在这个过程中,血管内皮是血管功能的关键调节因子,它既能促进血管内环境稳态的维持,也能推动血管疾病的发展。在过去30年里,膳食中ω-3(n-3)多不饱和脂肪酸的摄入——主要来源于鱼类——已成为一种通过对动脉粥样硬化各个阶段产生有益影响来改变心血管疾病风险的重要方式。本综述特别关注n-3脂肪酸对动脉粥样硬化早期和晚期分子事件的调节作用,包括对内皮细胞黏附分子表达以及促炎和促血管生成酶的影响。通过在内皮细胞膜磷脂中蓄积,ω-3脂肪酸已被证明可通过降低转录因子核因子-κB系统的激活来减少多个基因的转录激活。这是细胞内活性氧生成减少的继发结果。这一系列研究构成了营养基因组学的一个清晰范例,即营养素如何影响基因表达,最终影响广泛的人类疾病。