Artery Research (Dec 2020)
P.57 Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiac Remodelling in a Mouse Model of Advanced Atherosclerosis
Abstract
Background: Acetylsalicylic acid (ASA) is used in secondary prevention of cardiovascular disease (CVD) because of its antithrombotic effects. We investigated whether ASA has additional therapeutic value by preventing the progression of inflammation and cardiovascular remodelling in mice with stable atherosclerosis (ApoE−/−) and in a model of arterial stiffness with advanced unstable atherosclerotic plaques (ApoE−/−Fbn1C1039G+/− mice). Methods: Female ApoE−/− and ApoE−/−Fbn1C1039G+/− mice were fed a Western diet (WD). At 10 weeks WD, the mice were divided in 2 groups receiving ASA (5 mg/kg/day) via the drinking water or plain water (control) for a period of 15 weeks. Echocardiograms were performed at 10, 17 and 25 weeks WD. At the end, blood pressure was measured via tail-cuff and blood samples were taken. The aorta and heart were collected for histology. Results: ApoE−/−Fbn1C1039G+/− mice showed an increased neutrophil-lymphocyte ratio (NLR), an important inflammatory biomarker, which was decreased by ASA treatment (Table 1). Wall thickness of the proximal ascending aorta was reduced and elastin/collagen ratio was increased in ASA-treated ApoE−/−Fbn1C1039G+/− mice, resembling values measured in ApoE−/− mice (Table 1). Systolic blood pressure, cardiac fibrosis and hypertrophy (Table 1, Figure 1) were reduced after ASA treatment in ApoE−/−Fbn1C1039G+/− mice. ApoE−/− ApoE−/−Fbn1C1039G+/− Control ASA Control ASA Mean ± SEM N Mean ± SEM N Mean ± SEM N Mean ± SEM N Blood Neutrophils (%) 10.7 ± 2.1 15 9.1 ± 1.5 12 26.4 ± 6.2** 10 13.2 ± 2.1§ 7 Lymphocytes (%) 79.2 ± 3.0 15 80.0 ± 4.3 13 58.2 ± 7.9** 10 86.4 ± 2.4§§ 7 NLR 0.12 ± 0.02 14 0.12 ± 0.02 12 0.45 ± 0.13*** 9 0.16 ± 0.03§§ 7 Proximal aorta Wall thickness (μm) 64.9 ± 1.5 9 61.7 ± 1.8 10 70.0 ± 2.4 13 60.3 ± 2.9§§ 15 Elastin wall (%) 24.1 ± 1.2 9 28.0 ± 1.2 10 19.9 ± 1.1* 13 22.8 ± 1.5 15 Collagen wall (%) 44.4 ± 4.5 9 39.4 ± 3.2 10 63.9 ± 3.9** 13 47.1 ± 3.3§§ 15 Elastin/collagen ratio (%) 58.8 ± 5.9 9 75.1 ± 6.9* 10 32.5 ± 2.6*** 13 49.5 ± 2.1§§§ 15 Heart Heart weight/body weight (%) 0.50 ± 0.02 15 0.49 ± 0.02 14 1.16 ± 0.12*** 10 0.76 ± 0.05§§§ 8 Total fibrosis (%) 5.7 ± 0.2 15 6.1 ± 0.4 14 9.0 ± 0.7*** 16 6.1 ± 0.5§§§ 15 BP Systolic BP (mmHg) 88 ± 4 15 80 ± 4 12 83 ± 6 7 67 ± 4§ 8 Diastolic BP (mmHg) 63 ± 4 15 56 ± 3 12 59 ± 6 7 47 ± 4 8 2-way ANOVA followed by a simple main effects analysis including a Bonferroni correction for multiple comparisons: *p < 0.05, **p < 0.01, ***p < 0.001 vs. ApoE−/− control and §p < 0.05, §§p < 0.01, §§§p < 0.001 vs. ApoE−/−Fbnl C1039G+/− control. NLR, neutrophillymphocyte ratio; BP, blood pressure. Table 1Summary of main results Conclusion: We showed that ASA is able to decrease the NLR, passive aortic wall stiffness and cardiac remodelling in mice with advanced atherosclerosis to levels observed in mice with smaller and more stable atherosclerotic plaques. These data point towards an additional benefit of ASA in the prevention of CVD beyond its classical use.
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