Aims Whether and how iron affects the progression of atherosclerosis remains highly debated. Here, we investigate susceptibility to atherosclerosis in a mouse model (ApoE−/− FPNwt/C326S), which develops the disease in the context of elevated non-transferrin bound serum iron (NTBI). Methods and results Compared with normo-ferremic ApoE−/− mice, atherosclerosis is profoundly aggravated in iron-loaded ApoE−/− FPNwt/C326S mice, suggesting a pro-atherogenic role for iron. Iron heavily deposits in the arterial media layer, which correlates with plaque formation, vascular oxidative stress and dysfunction. Atherosclerosis is exacerbated by iron-triggered lipid profile alterations, vascular permeabilization, sustained endothelial activation, elevated pro-atherogenic inflammatory mediators, and reduced nitric oxide availability. NTBI causes iron overload, induces reactive oxygen species production and apoptosis in cultured vascular cells, and stimulates massive MCP-1-mediated monocyte recruitment, well-established mechanisms contributing to atherosclerosis. NTBI-mediated toxicity is prevented by transferrin- or chelator-mediated iron scavenging. Consistently, a low-iron diet and iron chelation therapy strongly improved the course of the disease in ApoE−/− FPNwt/C326S mice. Our results are corroborated by analyses of serum samples of haemochromatosis patients, which show an inverse correlation between the degree of iron depletion and hallmarks of endothelial dysfunction and inflammation. Conclusion Our data demonstrate that NTBI-triggered iron overload aggravates atherosclerosis and unravel a causal link between NTBI and the progression of atherosclerotic lesions. Our findings support clinical applications of iron restriction in iron-loaded individuals to counteract iron-aggravated vascular dysfunction and atherosclerosis.

Objectives: Empirical assessment of parental needs and affecting factors for counseling success after prenatal diagnosis of congenital heart disease (CHD). Methods: Counseling success after fetal diagnosis of CHD was assessed by a validated standardized questionnaire. The dependent variable "Effective Counseling" was measured in five created analytical dimensions (1. "Transfer of Medical Knowledge-ToMK"; 2. "Trust in Medical Staff-TiMS"; 3. "Transparency Regarding the Treatment Process-TrtTP"; 4. "Coping Resources-CR"; 5. "Perceived Situational Control-PSC"). Analyses were conducted with regard to influencing factors and correlations.

The objective of this study was to analyze parental counselling for fetal heart disease in an interdisciplinary and multicenter setting using a validated questionnaire covering medical, sociodemographic, and psychological aspects. n = 168 individuals were recruited from two pediatric heart centers and two obstetrics units. Overall, counselling was combined successful and satisfying in >99%; only 0.7% of parents were dissatisfied. "Perceived situational control" was impaired in 22.6%. Adequate duration of counselling leads to more overall counselling success (r = 0.368 ***), as well as providing written or online information (57.7% vs. 41.5%), which is also correlated to more "Transfer of Medical Knowledge" (r = 0.261 ***). Interruptions of consultation are negatively correlated to overall counselling success (r = −0.247 **) and to "Transparency regarding the Treatment Process" (r = −0.227 **). Lacking a separate counselling room is associated with lower counselling success for "Transfer of Medical Knowledge" (r = 0.210 ***). High-risk congenital heart disease (CHD) is correlated to lower counselling success (42.7% vs. 71.4% in low-risk CHD). A lack of parental language skills leads to less overall counselling success. There is a trend towards more counselling success for "Transfer of Medical Knowledge" after being counselled solely by cardiologists in one center (r = 0.208). Our results indicate that a structured approach may lead to more counselling success in selected dimensions. For complex cardiac malformations, counselling by cardiologists is essential. Parental "Perceived Situational Control" is often impaired, highlighting the need for further support throughout the pregnancy.