P.57 Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiac Remodelling in a Mouse Model of Advanced Atherosclerosis

DOI

10.2991/artres.k.201209.067How to use a DOI?

Keywords

Aspirin; fibrosis; inflammation; hypertrophy

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^−/−Fbn1^C1039G+/− mice).

Methods: Female ApoE^−/− and ApoE^−/−Fbn1^C1039G+/− 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^−/−Fbn1^C1039G+/− 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^−/−Fbn1^C1039G+/− 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^−/−Fbn1^C1039G+/− 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 1

Summary 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.

Copyright

© 2020 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - JOUR
AU  - Lynn Roth
AU  - Wim Martinet
AU  - Guido R.Y. De Meyer
PY  - 2020
DA  - 2020/12/31
TI  - P.57 Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiac Remodelling in a Mouse Model of Advanced Atherosclerosis
JO  - Artery Research
SP  - S79
EP  - S80
VL  - 26
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.201209.067
DO  - 10.2991/artres.k.201209.067
ID  - Roth2020
ER  -