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 deficien...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/1/404 |
| Summary: | 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 (<i>ApoE<sup>−/−</sup></i>) mice, a model of stable atherosclerosis, and in <i>ApoE<sup>−/−</sup></i> mice with a mutation in the fibrillin-1 gene (<i>Fbn1<sup>C1039G+/−</sup></i>), which is a model of elastic fibre fragmentation, accompanied by exacerbated unstable atherosclerosis. Female <i>ApoE<sup>−/−</sup></i> and <i>ApoE<sup>−/−</sup>Fbn1<sup>C1039G+/−</sup></i> 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 (<i>ApoE<sup>−/−</sup></i> (<i>n</i> = 14), <i>ApoE<sup>−/−</sup>Fbn1<sup>C1039G+/−</sup></i> (<i>n</i> = 19)) or plain drinking water (<i>ApoE<sup>−/−</sup></i> (<i>n</i> = 15), <i>ApoE<sup>−/−</sup>Fbn1<sup>C1039G+/−</sup></i> (<i>n</i> = 21)) for 15 weeks. <i>ApoE<sup>−/−</sup>Fbn1<sup>C1039G+/−</sup></i> mice showed an increased neutrophil–lymphocyte ratio (NLR) compared to <i>ApoE<sup>−/−</sup></i> mice, and this effect was normalised by ASA. In the proximal ascending aorta wall, ASA-treated <i>ApoE<sup>−/−</sup>Fbn1<sup>C1039G+/−</sup></i> mice showed less p-SMAD2/3 positive nuclei, a lower collagen percentage and an increased elastin/collagen ratio, consistent with the values measured in <i>ApoE<sup>−/−</sup></i> mice. ASA did not affect plaque progression, incidence of myocardial infarction and survival of <i>ApoE<sup>−/−</sup>Fbn1<sup>C1039G+/−</sup></i> mice, but systolic blood pressure, cardiac fibrosis and hypertrophy were reduced. In conclusion, ASA normalises the NLR, passive wall stiffness and cardiac remodelling in <i>ApoE<sup>−/−</sup>Fbn1<sup>C1039G+/−</sup></i> mice to levels observed in <i>ApoE<sup>−/−</sup></i> mice, indicating additional therapeutic benefits of ASA beyond its classical use. |
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| ISSN: | 1661-6596 1422-0067 |