RESUMO
OBJECTIVES: We aimed to investigate the relationship between dietary flavonoids, the dietary inflammatory index (DII), blood lead levels, and stroke and evaluate how these factors interact with one another in relation to stroke. MATERIALS AND METHODS: We analyzed data from 3675 older American adults aged ≥60 years, obtained from the National Health and Nutrition Examination Survey. Since this database does not specifically differentiate between hemorrhagic and ischemic strokes, our data include both types. We utilized the DII to assess the inflammatory potential of the diet, calculated using 24 h dietary recalls. To determine the association between dietary flavonoids, blood lead levels, DII, and stroke, we performed multivariate logistic regression, subgroup analysis, and restricted cubic splines. We modeled additive interactions to assess the relationship between blood lead levels and DII. RESULTS: A high intake of flavonols, flavan-3-ols, and total flavonoids correlated negatively with stroke risk, whereas blood lead levels had a positive association. After adjusting for confounders, stroke risk was found to increase with higher DII. Restricted cubic splines analysis revealed that flavan-3-ols, total flavonoids, blood lead levels, and DII were linearly related to stroke, while the relationships with flavonoids and flavonols were nonlinear. Additionally, a significant interaction was detected between high DII and elevated blood lead levels in relation to stroke risk. CONCLUSIONS: Intake of flavan-3-ol, flavanols, and total flavonoids is negatively associated with stroke risk, while higher blood lead levels and DII are positively related to it. High DII and elevated blood lead levels interact synergistically to influence stroke risk.
RESUMO
The exact cause of atherosclerosis is not known, and therefore, the current treatment options are limited. The activation of endothelial cells by oxidized low-density lipoprotein (ox-LDL) plays a key role in the initiation and progression of atherosclerosis. Phoenixin-20 is one of the newly identified neuropeptides with pleiotropic effects in the regulation of reproduction and other biological functions. G-protein receptor-coupled 173 (GPR173) is the putative receptor of Phoenixin-20. In the present study, we show that endothelial GPR173 is repressed upon ox-LDL stimulation in human aortic endothelial cells (HAECs). We further elaborate on the hypothesis that GPR173 could be involved in the pathogenesis of atherosclerosis through a series of experiments. Our results indicate that ox-LDL remarkably triggers the increase of ROS, NOX-4, pro-inflammatory cytokines IL-1ß, IL-8, and MCP-1 expression, as well as adhesion molecules ICAM-1 and VCAM-1 release. However, the agonism of GPR173 using Phoenixin-20 significantly ameliorates all of these harmful effects from ox-LDL by suppressing the NF-κB pathway. Furthermore, we show that agonism of GPR173 by Phoenixin-20 prevents the attachment of monocytes THP-1 to endothelial cells, which is an important therapeutic approach to preventing atherogenesis. In conclusion, our study demonstrates that GPR173 agonism by Phoenixin-20 plays a protective role against ox-LDL-induced endothelial dysfunction, implying that Phoenixin-20 may have therapeutic implications in atherosclerosis.
