Linking CD11b +

Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (sub)populations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE−/−) mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b+ conventional dendritic cell (cDC) subset in the plaque. Secondly, a strong inverse correlation was observed between CD11b+ cDC or natural killer T (NKT) cells in blood and markers of inflammation in the plaque (including CD3, T-bet, CCR5, and CCR7). This indicates that circulating CD11b+ cDC and NKT cells show great potential to reflect the inflammatory status in the atherosclerotic plaque. Our results suggest that distinct changes in inflammatory cell dynamics may carry biomarker potential reflecting atherosclerotic lesion progression. This not only is crucial for a better understanding of the immunopathogenesis but also bares therapeutic potential, since immune cell-based therapies are emerging as a promising novel strategy in the battle against atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in atherosclerosis serves as a good candidate for future investigations

Acetylsalicylic acid reduces passive aortic wall stiffness and cardiovascular remodelling in a mouse model of advanced atherosclerosis

Acetylsalicylic acid (ASA) is widely used in secondary prevention of cardiovascular (CV) disease, mainly because of its antithrombotic effects. Here, we investigated whether ASA can prevent the progression of vessel wall remodelling, atherosclerosis, and CV complications in apolipoprotein E deficient (ApoE(−/−)) mice, a model of stable atherosclerosis, and in ApoE(−/−) mice with a mutation in the fibrillin-1 gene (Fbn1(C1039G+/−)), which is a model of elastic fibre fragmentation, accompanied by exacerbated unstable atherosclerosis. Female ApoE(−/−) and ApoE(−/−)Fbn1(C1039G+/−) mice were fed a Western diet (WD). At 10 weeks of WD, the mice were randomly divided into four groups, receiving either ASA 5 mg/kg/day in the drinking water (ApoE(−/−) (n = 14), ApoE(−/−)Fbn1(C1039G+/−) (n = 19)) or plain drinking water (ApoE(−/−) (n = 15), ApoE(−/−)Fbn1(C1039G+/−) (n = 21)) for 15 weeks. ApoE(−/−)Fbn1(C1039G+/−) mice showed an increased neutrophil–lymphocyte ratio (NLR) compared to ApoE(−/−) mice, and this effect was normalised by ASA. In the proximal ascending aorta wall, ASA-treated ApoE(−/−)Fbn1(C1039G+/−) mice showed less p-SMAD2/3 positive nuclei, a lower collagen percentage and an increased elastin/collagen ratio, consistent with the values measured in ApoE(−/−) mice. ASA did not affect plaque progression, incidence of myocardial infarction and survival of ApoE(−/−)Fbn1(C1039G+/−) mice, but systolic blood pressure, cardiac fibrosis and hypertrophy were reduced. In conclusion, ASA normalises the NLR, passive wall stiffness and cardiac remodelling in ApoE(−/−)Fbn1(C1039G+/−) mice to levels observed in ApoE(−/−) mice, indicating additional therapeutic benefits of ASA beyond its classical use