PMID- 23557933 OWN - NLM STAT- MEDLINE DCOM- 20131108 LR - 20220408 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 72 DP - 2013 Jun TI - 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. PG - 69-82 LID - S1043-6618(13)00060-1 [pii] LID - 10.1016/j.phrs.2013.03.011 [doi] AB - 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-1beta and TNF-alpha 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. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Tome-Carneiro, Joao AU - Tome-Carneiro J AD - Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain. FAU - Larrosa, Mar AU - Larrosa M FAU - Yanez-Gascon, Maria J AU - Yanez-Gascon MJ FAU - Davalos, Alberto AU - Davalos A FAU - Gil-Zamorano, Judit AU - Gil-Zamorano J FAU - Gonzalvez, Manuel AU - Gonzalvez M FAU - Garcia-Almagro, Francisco J AU - Garcia-Almagro FJ FAU - Ruiz Ros, Jose A AU - Ruiz Ros JA FAU - Tomas-Barberan, Francisco A AU - Tomas-Barberan FA FAU - Espin, Juan Carlos AU - Espin JC FAU - Garcia-Conesa, Maria-Teresa AU - Garcia-Conesa MT LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130401 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cytokines) RN - 0 (MicroRNAs) RN - 0 (Plant Extracts) RN - 0 (Stilbenes) RN - Q369O8926L (Resveratrol) SB - IM MH - Aged MH - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use MH - Coronary Artery Disease/complications/*diet therapy/genetics/immunology MH - Cytokines/*genetics/immunology MH - Diabetes Mellitus, Type 2/complications/*diet therapy/genetics/immunology MH - Dietary Supplements/analysis MH - Gene Expression Regulation/drug effects MH - Humans MH - Hypertension/complications/*diet therapy/genetics/immunology MH - Inflammation/drug therapy/genetics/immunology MH - Leukocytes, Mononuclear/*drug effects/immunology/metabolism MH - Male MH - MicroRNAs/*genetics MH - Middle Aged MH - Models, Molecular MH - Plant Extracts/therapeutic use MH - Resveratrol MH - Stilbenes/*therapeutic use MH - Transcriptome/drug effects MH - Vitis/chemistry EDAT- 2013/04/06 06:00 MHDA- 2013/11/10 06:00 CRDT- 2013/04/06 06:00 PHST- 2013/02/20 00:00 [received] PHST- 2013/03/25 00:00 [revised] PHST- 2013/03/25 00:00 [accepted] PHST- 2013/04/06 06:00 [entrez] PHST- 2013/04/06 06:00 [pubmed] PHST- 2013/11/10 06:00 [medline] AID - S1043-6618(13)00060-1 [pii] AID - 10.1016/j.phrs.2013.03.011 [doi] PST - ppublish SO - Pharmacol Res. 2013 Jun;72:69-82. doi: 10.1016/j.phrs.2013.03.011. Epub 2013 Apr 1.