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2015年1月9日 讯 /生物谷BIOON/ –尽管有研究显示，高脂肪饮食和特定细菌的暴露会引发机体动脉粥样硬化，但近日一篇刊登于国际杂志BMC Genomics上的研究论文中，来自波士顿大学医学中心的研究人员通过研究首次鉴别出了因不同刺激影响而改变的不同的基因路径，相关研究为开发治疗疾病的个体化疗法提供了新的思路和希望。
动脉粥样硬化是一种和心衰及中风相关的常见人类疾病，而特定的细菌和高脂饮食往往和动脉粥样硬化发病风险直接相关，研究人员曾经在牙周病患者的口腔中发现了一种名为牙龈卟啉单胞菌的细菌，以及一种引发肺炎的肺炎衣原体。
这项研究中，研究人员利用四组实验组进行研究，对比了其在血管组织中全基因组表达的改变，第一组研究对象接受牙龈卟啉单胞菌，第二组研究对象接受肺炎衣原体，第三组进行高脂饮食，第四组作为对照组；随后研究人员利用全基因组芯片分析对四组研究对象的血管组织进行分析，来揭示每组研究对象动脉粥样硬化斑块基因通路的改变。
最后研究人员Caroline Attardo Genco说道，人类机体的动脉粥样硬化的发生远比我们想象中复杂，本文研究结果或可帮助我们解释为何特殊的感染和高脂饮食会引发机体产生动脉粥样硬化斑块。（生物谷Bioon.com）
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Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet.
Carolyn D Kramer, Ellen O Weinberg, Adam C Gower, Xianbao He, Samrawit Mekasha, Connie Slocum, Lea M Beaulieu, Lee Wetzler, Yuriy Alekseyev, Frank C Gibson, Jane E Freedman, Robin R Ingalls and Caroline A Genco
Background Atherosclerosis is a progressive disease characterized by inflammation and accumulation of lipids in vascular tissue. Porphyromonas gingivalis (Pg) and Chlamydia pneumoniae (Cp) are associated with inflammatory atherosclerosis in humans. Similar to endogenous mediators arising from excessive dietary lipids, these Gram-negative pathogens are pro-atherogenic in animal models, although the specific inflammatory/atherogenic pathways induced by these stimuli are not well defined. In this study, we identified gene expression profiles that characterize P. gingivalis, C. pneumoniae, and Western diet (WD) at acute and chronic time points in aortas of Apolipoprotein E (ApoE-/-) mice. Results At the chronic time point, we observed that P. gingivalis was associated with a high number of unique differentially expressed genes compared to C. pneumoniae or WD. For the top 500 differentially expressed genes unique to each group, we observed a high percentage (76%) that exhibited decreased expression in P. gingivalis-treated mice in contrast to a high percentage (96%) that exhibited increased expression in WD mice. C. pneumoniae treatment resulted in approximately equal numbers of genes that exhibited increased and decreased expression. Gene Set Enrichment Analysis (GSEA) revealed distinct stimuli-associated phenotypes, including decreased expression of mitochondrion, glucose metabolism, and PPAR pathways in response to P. gingivalis but increased expression of mitochondrion, lipid metabolism, carbohydrate and amino acid metabolism, and PPAR pathways in response to C. pneumoniae; WD was associated with increased expression of immune and inflammatory pathways. DAVID analysis of gene clusters identified by two-way ANOVA at acute and chronic time points revealed a set of core genes that exhibited altered expression during the natural progression of atherosclerosis in ApoE-/- mice; these changes were enhanced in P. gingivalis-treated mice but attenuated in C. pneumoniae-treated mice. Notable differences in the expression of genes associated with unstable plaques were also observed among the three pro-atherogenic stimuli. Conclusions Despite the common outcome of P. gingivalis, C. pneumoniae, and WD on the induction of vascular inflammation and atherosclerosis, distinct gene signatures and pathways unique to each pro-atherogenic stimulus were identified. Our results suggest that pathogen exposure results in dysregulated cellular responses that may impact plaque progression and regression pathways.