Atherosclerosis leading to cardiovascular diseases remains a dominant medical problem. In the early stages of this disease, the interaction between circulating monocytes and the endothelium is crucial. Monocytes and macrophages express scavenger receptor A (SR-A), which mediates cell adhesion and subsequently uptake of oxidized low-density lipoproteins (LDL). High iron stores in monocytes or macrophages are known to predispose individuals to atherosclerosis, however the reasons remain poorly understood. We hypothesized that a combination of iron and LDL may induce proatherogenic changes in circulating monocytes. Here, we treated a human monocytic cell line THP-1 with isolated LDL and/or iron. A limited uptake of native LDL, but not iron or oxidized LDL, markedly induced expression of SR-A in these cells. Both SR-AI and SR-AII isoforms were upregulated. The increased SR-A was also seen at the protein level, and LDL treatment increased cellular adhesion. The induction of SR-A by LDL was inhibited by the lysosomotropic thiol WR-1065 and by the chain-breaking lipophilic antioxidant butylated hydroxytoluene (BHT). The fluorescent probe BODIPY C11 exhibited increased lipid peroxidation inside lysosomes after LDL administration. The induction of SR-A by LDL was blocked by two silencing RNAs directed against the nuclear coactivator receptor NCOA4, the cargo receptor necessary for the autophagy of ferritin. These results may point to a new pathogenetic mechanism of early-stage atherosclerosis, in which high iron stores in circulating monocytes, through increased lysosomal lipid peroxidation, may lead to an upregulated expression of SR-A, which makes the cells more adhesive and hence more atherogenic.

• Keywords
• atherosclerosis, ferritinophagy, lipid peroxidation, lysosome, redox‐active iron,
• MeSH
• Atherosclerosis metabolism   MeSH
• Cell Adhesion MeSH
• Humans MeSH
• Lipoproteins, LDL * metabolism   MeSH
• Lysosomes * metabolism   MeSH
• Monocytes * metabolism   MeSH
• Oxidation-Reduction MeSH
• Scavenger Receptors, Class A * metabolism   genetics   MeSH
• THP-1 Cells MeSH
• Iron * metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Lipoproteins, LDL * MeSH
• oxidized low density lipoprotein MeSH Browser
• Scavenger Receptors, Class A * MeSH
• Iron * MeSH

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

• MeSH
• Biomarkers blood   MeSH
• Endothelium, Vascular physiopathology   MeSH
• Cystic Fibrosis blood   diagnosis   physiopathology   MeSH
• Child MeSH
• Adult MeSH
• Hyperemia * MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Case-Control Studies MeSH
• Age Factors MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Biomarkers MeSH

The prevalence of cardiovascular disease (CVD) is rising worldwide, remaining the major cause of death in developed countries. Polyphenols have been shown to have cardioprotective properties; however, their impact on iron bioavailability and potential impact on other aspects of health is unclear. A systematic review was undertaken to evaluate the current status of the relationship between habitual polyphenol consumption, iron status, and circulating biomarkers of CVD. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines, searches were performed across 5 electronic databases (PubMed, Cochrane Library, Scopus, Web of Science, and CINAHL) to identify randomized controlled trials which investigated the effects of polyphenol consumption on inflammatory markers, serum lipid profile, and iron absorption and bioavailability. In total, 1174 records were identified, with only 7 studies meeting the inclusion criteria. The selected studies involved 133 participants and used a variety of foods and supplements, including olive oil and cherries, rich in polyphenols including hydroxytyrosol, quercetin, and resveratrol, as well as catechin enriched drinks. The duration of the studies ranged from between 56 and 145 days, with total polyphenolic content of the food items and supplements ranging from 45 to 1015 mg (per 100 g). Polyphenols did not appear to interfere with iron status, and most studies reported improvements in inflammatory markers and lipid profile. While these results are promising, the limited number of studies and considerable heterogeneity across the interventions support the need for more extensive trials assessing the relationship between polyphenol intake, iron bioavailability, and CVD risk.

• Keywords
• CVD, Polyphenol, atherosclerosis, iron status,
• Publication type
• Journal Article MeSH
• Review MeSH