10 research outputs found
Specialized proresolving mediators protect against experimental autoimmune myocarditis by modulating Ca2+ handling and NRF2 activation
Preclinical research[Abstract] Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulumâadenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.Ministerio de EconomĂa y Competitividad (España); SAF-2017-84777RInstituto de Salud Carlos III; PI17/01093Instituto de Salud Carlos III; PI17/01344Instituto de Salud Carlos III; PI20/01482Ministerio de Ciencia, InnovaciĂłn y Universidades (España); PGC2018-097019-B-I00Ministerio de EconomĂa, Industria y Competitividad (España); 10.13039/501100011033Ministerio de Industria, EconomĂa y Competitividad; PID2020-113238RB-I00Ministerio de Industria, EconomĂa y Competitividad (España); PID2019-105600RB-I00FundaciĂłn La Caixa; HR17-0024
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Dietary αâLinolenic Acid, Marine Ïâ3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvenciĂłn con DIeta MEDiterrĂĄnea (PREDIMED) Study
Background: Epidemiological evidence suggests a cardioprotective role of αâlinolenic acid (ALA), a plantâderived Ïâ3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine Ïâ3 fatty acids (longâchain nâ3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to allâcause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for longâchain nâ3 polyunsaturated fatty acids (â„500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvenciĂłn con DIeta MEDiterrĂĄnea (PREDIMED) trial. Multivariableâadjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9ây followâup, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56â0.92) for allâcause mortality and 0.95 (95% CI 0.58â1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for longâchain nâ3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67â1.05) for allâcause mortality, 0.61 (95% CI 0.39â0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29â0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22â1.01) for sudden cardiac death. The highest reduction in allâcause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45â0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to allâcause mortality, whereas protection from cardiac mortality is limited to fishâderived longâchain nâ3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639
Interplay of walnut consumption, changes in circulating miRNAs and reduction in LDL-cholesterol in elders
The mechanisms underlying the lipid-lowering effect of nuts remain elusive. This study explores whether one-year supplementation with walnuts decreases LDL-cholesterol (LDL-C) by affecting the expression of circulating microRNAs (c-miRNA). In this sub-study of the Walnuts and Healthy Aging (WAHA) trial, we obtained fasting serum at baseline and at 1 year from 330 free-living participants (63-79 year, 68% women), allocated into a control group (CG, abstinence from walnuts, n = 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30-60 g/d, n = 166). Participants in the WG showed a 1 year decrease in LDL-C (-9.07, (95% confidence interval: -12.87; -5.73) mg/dL; p = 0.010 versus changes in the CG). We conducted a miRNA array in eight randomly selected participants in the WG who decreased in LDL-C. This yielded 53 c-miRNAs with statistically significant changes, 27 of which survived the correction for multiple testing. When validating them in the full population, statistical significance lasted for hsa-miR-551a, being upregulated in the WG. In mediation analysis, the change in hsa-miR-551a was unrelated to LDL-C decrease. Long-term supplementation with walnuts decreased LDL-C independently of the changes in c-miRNA. The hsa-miR-551a upregulation, which has been linked to a reduced cell migration and invasion in several carcinomas, suggests a novel mechanism of walnuts in cancer risk.This work was supported by a grant from the California Walnut Commission, Folsom, CA, US (to J.S. and E.R.), by a âManuel de Hoyaâ grant (2014) from the Sociedad Española de Arteriosclerosis, and by Fondo de InvestigaciĂłn SanitariaâFondo Europeo de Desarrollo Regional (grant no. PI15/01014) (all to A.S.-V.). M.-C.L.d.l.H. was supported by a post-doctoral research contract funded by the community of Madrid and the European Union (PEJD-2016/BIO-2781). A.G.-R. acknowledges the Marie Curie AMAROUT-II Europe Program. A.D. was supported by the Spanish Agencia Estatal de InvestigaciĂłn and European Feder Funds (AGL2016-78922-R) and FundaciĂłn RamĂłn Areces (CIVP18A3888), Madrid, Spain. These funding agencies had no input in the study design, data collection, analyses, or writing and submission of the manuscript