Dejeans N, Auclair S, Chauvet S, Milenkovic D, Mazur A
INRA, Unite de Nutrition Humaine, UMR 1019, Clermont-Fd/Theix, and CRNH d'Auvergne, 63122 St Genes Champanelle, France.
J Physiol Pharmacol. 2009 May;60 Suppl 1:37-45.
High-density microarrays were recently used to identify the genomic profiles of vascular cells during atherogenesis. This strategy succeeded in identifying both biomarkers and underlying biological processes of the pathological development. However, data documenting the early stages of disease are sparse. To identify the mechanisms involved in atherogenesis, we examined differential gene expression in the aorta of C57BL/6J mice fed a high-fat diet (HFD) or a low-fat diet (LFD), for a short period of time of three weeks. The cDNAmicroarray analysis revealed that the expression of 448 genes was significantly different between the two groups. As expected, key genes involved in lipid synthesis or catabolism were down- and upregulated, respectively, representing a normal gene expression response to increased cellular lipid levels. Overrepresented biological processes were identified by Gene Ontology (GO) analysis, which revealed that aortic cells differentiate into a new phenotype in mice fed the HFD. This phenotype was represented by changes in the expression of 81 genes associated with extracellular matrix and cytoskeletal modifications. Some of these genes were previously shown to be involved in the cardiovascular diseases process. In conclusion, short-term HFD consumption results in metabolic disturbances leading to a broad induction of genes involved in vessel architecture remodelling.
高密度微阵列最近被用于识别动脉粥样硬化形成过程中血管细胞的基因组图谱。这一策略成功地识别出了病理发展的生物标志物和潜在生物学过程。然而,记录疾病早期阶段的数据很少。为了识别动脉粥样硬化形成所涉及的机制,我们在短期(三周)内检查了喂食高脂饮食(HFD)或低脂饮食(LFD)的C57BL/6J小鼠主动脉中的差异基因表达。cDNA微阵列分析显示,两组之间448个基因的表达存在显著差异。正如预期的那样,参与脂质合成或分解代谢的关键基因分别下调和上调,这代表了对细胞脂质水平升高的正常基因表达反应。通过基因本体论(GO)分析确定了过度表达的生物学过程,结果显示喂食HFD的小鼠主动脉细胞分化为一种新的表型。这种表型表现为与细胞外基质和细胞骨架修饰相关的81个基因的表达变化。其中一些基因先前已被证明参与心血管疾病过程。总之,短期食用HFD会导致代谢紊乱,从而广泛诱导参与血管结构重塑的基因。