Extracellular matrix (ECM) remodelling is critical in abdominal aortic aneurysm (AAA), a life-threatening condition lacking effective pharmacotherapy. However, key ECM components regulating vascular i Show more
Extracellular matrix (ECM) remodelling is critical in abdominal aortic aneurysm (AAA), a life-threatening condition lacking effective pharmacotherapy. However, key ECM components regulating vascular integrity and remodelling remain poorly understood. Transcriptome profiling and studies in human AAA and in aneurysms from two models susceptible to angiotensin II (Ang II)-induced AAA-apolipoprotein E knockout mice (ApoE Transcriptome profiling highlighted the relevance of the ECM-mediated pathway and the upregulation of THBS4 in human AAA. In a large cohort of patients and donors and in Ang II-infused ApoE We uncover the early and sustained induction of TSP4 in AAA and its protective role in limiting vascular inflammation and destructive remodelling. Modulation of TSP4-dependent pathways may represent a novel avenue to improve vascular stability in AAA. Show less
Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsat Show more
Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsaturated fatty acids but, in contrast, higher circulating linoleic acid (LA) levels-reflective of dietary LA intake, are associated with a reduced risk of type 2 diabetes. However, genetic variants in the fatty acid desaturase 1 gene (FADS1) may influence individual responses to plant-based fats. We explored whether FADS1 variants influence the relationships of LA and α-linolenic acid (ALA) intakes and nut consumption with plasma phospholipid fatty acid profiles and type 2 diabetes risk in a large-scale cohort study and a randomized controlled trial. In the EPIC-InterAct case-cohort (7,498 type 2 diabetes cases, 10,087 subcohort participants), we investigated interactions of dietary and plasma phospholipid fatty acids and nut consumption with FADS1 rs174547 in relation to incident type 2 diabetes using weighted Cox regression. In PREDIMED (492 participants in the Mediterranean Diet + Nuts intervention group, 436 participants in the control group), we compared changes in plasma phospholipid FAs from baseline to year 1. In EPIC-InterAct and PREDIMED, nut consumption was positively associated with LA plasma levels and inversely with arachidonic acid, the latter becoming stronger with increasing number of the minor rs174547 C allele (p interaction EPIC-InterAct: 0.030, PREDIMED: 0.003). Although the inverse association of nut consumption with diabetes seemed stronger in participants with rs174547 CC-genotype (HR: 0.73, 95% CI: 0.54-1.00) compared with CT (0.94, 0.81-1.10) or TT (0.90, 0.78-1.05) in EPIC-InterAct, this interaction was not statistically significant. FADS1 variation modified the effect of nut consumption on circulating FAs. We did not observe clear evidence that it modified the association between nut consumption and type 2 diabetes risk. Show less