Flavanol Consumption in Healthy Men Preserves Integrity of Immunological-Endothelial Barrier Cell Functions: Nutri(epi)genomic Analysis.
Flavanol Consumption in Healthy Men Preserves Integrity of Immunological-Endothelial Barrier Cell Functions: Nutri(epi)genomic Analysis.
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DOI：
10.1002/mnfr.202100991
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发表时间：
2022-11
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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虽然可可黄烷醇（CF）的摄入可以改善心血管风险生物标志物，但其保护作用的分子机制尚不清楚。研究CF的营养（epi）基因组效应，并确定可能介导血管健康益处的调节网络。20名健康的中年男性服用CF（每日两次450毫克）或对照饮料1个月。微阵列分析鉴定了2235个差异表达基因（DEG）参与调节免疫反应、细胞粘附或细胞骨架组织的过程。不同的DEG模式与CF相关的内皮功能、动脉硬度和血压变化相关。DEG谱与心血管疾病患者表达谱呈负相关。CF调节基因的DNA甲基化谱与细胞粘附、肌动蛋白细胞骨架组织或细胞信号传导有关。硅对接分析表明，CF代谢物具有与细胞信号蛋白和转录因子结合的潜力。CF消耗后获得的血浆孵育降低单核细胞对内皮细胞的粘附，并剂量依赖性地增加循环血管生成细胞的一氧化氮依赖性趋化性，进一步验证了CF代谢物的生物学功能。在健康人群中，CF消费可能通过调节基因表达和DNA甲基化来调节血管保护作用，从而达到心血管保护作用，这与临床结果一致，通过保持免疫-内皮屏障功能的完整性。健康中年男性摄入可可黄烷醇（CF）可调节循环免疫细胞的整体基因表达和DNA甲基化谱。已鉴定的基因参与免疫应答、细胞粘附或细胞骨架组织的调节。这些结果揭示了CF可能介导血管保护作用的分子机制，与临床结果一致，通过保持内皮屏障功能的完整性。
While cocoa flavanol (CF) consumption improves cardiovascular risk biomarkers, molecular mechanisms underlying their protective effects are not understood. To investigate nutri(epi)genomic effects of CF and identify regulatory networks potential mediating vascular health benefits. Twenty healthy middle‐aged men consume CF (bi‐daily 450 mg) or control drinks for 1 month. Microarray analysis identifies 2235 differentially expressed genes (DEG) involved in processes regulating immune response, cell adhesion, or cytoskeleton organization. Distinct patterns of DEG correlate with CF‐related changes in endothelial function, arterial stiffness, and blood pressure. DEG profile negatively correlates with expression profiles of cardiovascular disease patients. CF modulated DNA methylation profile of genes implicates in cell adhesion, actin cytoskeleton organization, or cell signaling. In silico docking analyses indicate that CF metabolites have the potential of binding to cell signaling proteins and transcription factors. Incubation of plasma obtained after CF consumption decrease monocyte to endothelial adhesion and dose‐dependently increase nitric oxide‐dependent chemotaxis of circulating angiogenic cells further validating the biological functions of CF metabolites. In healthy humans, CF consumption may mediate vascular protective effects by modulating gene expression and DNA methylation towards a cardiovascular protective effect, in agreement with clinical results, by preserving integrity of immunological‐endothelial barrier functions. Consumption of cocoa flavanol (CF) by healthy middle‐aged men modulate global gene expression and DNA methylation profile in circulating immune cells. Identified genes are involved in regulation of immune response, cell adhesion, or cytoskeleton organization. These results reveal molecular mechanisms of CF which may mediate vascular protective effects, in agreement with clinical results, by preserving integrity of endothelial barrier functions.
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影响因子：
4.1
作者：
Feliciano, Rodrigo P.;Mecha, Elsa;Rodriguez-Mateos, Ana
通讯作者：
Rodriguez-Mateos, Ana
DOI：
10.1161/atvbaha.110.211581
发表时间：
2010-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Heiss C;Schanz A;Amabile N;Jahn S;Chen Q;Wong ML;Rassaf T;Heinen Y;Cortese-Krott M;Grossman W;Yeghiazarians Y;Springer ML
通讯作者：
Springer ML
影响因子：
3.7
作者：
Arking, Dan E.;Reinier, Kyndaron;Chugh, Sumeet S.
通讯作者：
Chugh, Sumeet S.
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
影响因子：
3.7
作者：
Crescenti A;Solà R;Valls RM;Caimari A;Del Bas JM;Anguera A;Anglés N;Arola L
通讯作者：
Arola L