Abstract
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 (Fbn1C1039G+/−), which is a model of elastic fibre fragmentation, accompanied by exacerbated unstable atherosclerosis. Female ApoE−/− and ApoE−/−Fbn1C1039G+/− 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−/−Fbn1C1039G+/− (n = 19)) or plain drinking water (ApoE−/− (n = 15), ApoE−/−Fbn1C1039G+/− (n = 21)) for 15 weeks. ApoE−/−Fbn1C1039G+/− 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−/−Fbn1C1039G+/− 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−/−Fbn1C1039G+/− 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−/−Fbn1C1039G+/− mice to levels observed in ApoE−/− mice, indicating additional therapeutic benefits of ASA beyond its classical use.
Highlights
Age-related diseases such as cardiovascular disease (CVD), have a substantial impact on our quality of life
Mortality, caused by sudden death of the mice during the timeframe of the treatment protocol, was significantly higher in apolipoprotein E deficient (ApoE−/−)Fbn1C1039G+/− mice compared to ApoE−/− mice, but was not affected by Acetylsalicylic acid (ASA) treatment (Table 1, Figure 1)
Heart and spleen weight in ApoE−/−Fbn1C1039G+/− mice were reduced as a result of ASA treatment (Table 1)
Summary
Age-related diseases such as cardiovascular disease (CVD), have a substantial impact on our quality of life. Vascular ageing is characterised by structural and functional changes in the wall of large arteries leading to arterial stiffness, thereby promoting atherosclerotic disease progression [1]. Atherosclerosis is a progressive inflammatory disease of the large and medium-sized arteries, characterised by the formation of plaques in the vessel wall. During the development of the disease, the stability of the atherosclerotic plaque plays a major role. When a plaque develops such an unstable phenotype, it may rupture, followed by thrombosis and clinical complications such as myocardial infarction (MI) and stroke [2,3,4]. Despite the significant therapeutic advances in cardiology over the past decades, atherosclerotic plaque rupture remains a leading cause of acute cardiovascular death. Delaying the process of vascular ageing and arterial stiffening might reduce the progression of atherosclerosis, thereby reducing the societal and economic burden of CVD
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