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Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis.

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 (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.

SUBMITTER: Roth L

PROVIDER: S-EPMC8745264 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). METHODS:MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57?±?0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. RESULTS:The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p?<?0.001), but there were no significant differences in AA distensibility (p?=?0.099), DA distensibility (p?=?0.498) or PWV (p?=?0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. CONCLUSIONS:In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. KEY POINTS:• Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I.

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Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis.

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