Massaro M, Scoditti E, Carluccio M A, Campana M C, De Caterina R
C.N.R. Institute of Clinical Physiology, Pisa, and Lecce, Italy.
Cell Mol Biol (Noisy-le-grand). 2010 Feb 25;56(1):59-82.
Atherosclerosis is now widely accepted to be an inflammatory disease, characterized by degenerative as well as proliferative changes and extracellular accumulation of lipid and cholesterol, in which an ongoing inflammatory reaction plays an important role both in initiation and progression/destabilization, converting a chronic process into an acute disorder. Neovascularization has also been recognized as an important process for the progression/destabilization of atherosclerotic plaques. In fact, vulnerable atherosclerotic plaques prone to rupture are characterized by an enlarged necrotic core, containing an increased number of vasa vasorum, apoptotic macrophages, and more frequent intraplaque haemorrhage. Various functional roles have been assigned to intimal microvessels, however the relationship between the process of angiogenesis and its causal association with the progression and complications of atherosclerosis are still challenging and controversial. 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, including plaque angiogenesis. 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 an attenuation of 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.
动脉粥样硬化现已被广泛认为是一种炎症性疾病，其特征为退行性和增殖性变化以及脂质和胆固醇的细胞外积聚，其中持续的炎症反应在疾病的起始和进展/失稳过程中均发挥重要作用，将慢性过程转变为急性病症。新生血管形成也被认为是动脉粥样硬化斑块进展/失稳的一个重要过程。事实上，易于破裂的易损动脉粥样硬化斑块的特征是坏死核心增大，含有数量增多的滋养血管、凋亡巨噬细胞，且斑块内出血更为频繁。内膜微血管具有多种功能作用，然而血管生成过程与其与动脉粥样硬化进展及并发症的因果关系仍具有挑战性且存在争议。在过去30年中，膳食中ω-3（n-3）多不饱和脂肪酸的摄入——主要来源于鱼类——已成为通过对动脉粥样硬化各个阶段（包括斑块血管生成）产生有益影响来改变心血管风险的一种重要方式。本综述特别关注n-3脂肪酸对动脉粥样硬化早期和晚期发生过程中涉及的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减弱转录因子核因子-κB系统的激活来降低多个基因的转录激活。这是由于细胞内活性氧生成减少所致。这一系列研究构成了营养基因组学的一个清晰例子——即营养素如何影响基因表达，最终影响广泛的人类疾病。
