title: One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.
abstract: Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8 mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients.
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain.
authors.forename: João
authors.initials: J
authors.lastname: Tomé-Carneiro
authors.forename: Mar
authors.initials: M
authors.lastname: Larrosa
authors.forename: María J
authors.initials: MJ
authors.lastname: Yáñez-Gascón
authors.forename: Alberto
authors.initials: A
authors.lastname: Dávalos
authors.forename: Judit
authors.initials: J
authors.lastname: Gil-Zamorano
authors.forename: Manuel
authors.initials: M
authors.lastname: Gonzálvez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: García-Almagro
authors.forename: José A
authors.initials: JA
authors.lastname: Ruiz Ros
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espín
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: García-Conesa
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000150:complications / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology; D019587:Dietary Supplements / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008958:Models, Molecular; D010936:Plant Extracts / Q000627:therapeutic use; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D059467:Transcriptome / Q000187:drug effects; D027843:Vitis / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D035683:MicroRNAs; D010936:Plant Extracts; D013267:Stilbenes; D000077185:Resveratrol