Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis
Abstract
:1. Introduction
2. Results
2.1. ASA Treatment Normalises Neutrophil–Lymphocyte Ratio in ApoE−/−Fbn1C1039G+/− Mice
2.2. Atherosclerotic Plaque Progression and the Occurrence of Myocardial Infarctions Are Not Affected by ASA
2.3. Passive Wall Stiffness Is Reduced in ASA-Treated ApoE−/−Fbn1C1039G+/− Mice
2.4. ASA Treatment Reduces Systolic Blood Pressure and Cardiac Remodelling in ApoE−/−Fbn1C1039G+/− Mice
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. Acetylsalicylic Acid Treatment
4.3. Echocardiography
4.4. Blood Pressure Measurements
4.5. Flow Cytometry
4.6. Histology
4.7. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Palombo, C.; Kozakova, M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul. Pharmacol. 2016, 77, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Lusis, A.J. Atherosclerosis. Nature 2000, 407, 233–241. [Google Scholar] [CrossRef]
- Libby, P. Mechanisms of acute coronary syndromes and their implications for therapy. N. Engl. J. Med. 2013, 368, 2004–2013. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yla-Herttuala, S.; Bentzon, J.F.; Daemen, M.; Falk, E.; Garcia-Garcia, H.M.; Herrmann, J.; Hoefer, I.; Jauhiainen, S.; Jukema, J.W.; Krams, R.; et al. Stabilization of atherosclerotic plaques: An update. Eur. Heart J. 2013, 34, 3251–3258. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ungvari, Z.; Tarantini, S.; Donato, A.J.; Galvan, V.; Csiszar, A. Mechanisms of Vascular Ageing. Circ. Res. 2018, 123, 849–867. [Google Scholar] [CrossRef]
- Mozos, I.; Malainer, C.; Horbanczuk, J.; Gug, C.; Stoian, D.; Luca, C.T.; Atanasov, A.G. Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases. Front. Immunol. 2017, 8, 1058. [Google Scholar] [CrossRef] [Green Version]
- Li, J.; Chen, Q.; Luo, X.; Hong, J.; Pan, K.; Lin, X.; Liu, X.; Zhou, L.; Wang, H.; Xu, Y.; et al. Neutrophil-to-Lymphocyte Ratio Positively Correlates to Age in Healthy Population. J. Clin. Lab. Anal. 2015, 29, 437–443. [Google Scholar] [CrossRef]
- Valiathan, R.; Ashman, M.; Asthana, D. Effects of Ageing on the Immune System: Infants to Elderly. Scand. J. Immunol. 2016, 83, 255–266. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.; Chen, X.; Huang, L.; Lu, J. Association between neutrophil–lymphocyte ratio and arterial stiffness in patients with acute coronary syndrome. Biosci. Rep. 2019, 39, 39. [Google Scholar] [CrossRef] [Green Version]
- Chen, C.; Cong, B.L.; Wang, M.; Abdullah, M.; Wang, X.L.; Zhang, Y.H.; Xu, S.J.; Cui, L. Neutrophil to lymphocyte ratio as a predictor of myocardial damage and cardiac dysfunction in acute coronary syndrome patients. Integr. Med. Res. 2018, 7, 192–199. [Google Scholar] [CrossRef]
- Ozyilmaz, S.; Akgul, O.; Uyarel, H.; Pusuroglu, H.; Gul, M.; Satilmisoglu, M.H.; Bolat, I.; Ozyilmaz, I.; Ucar, H.; Yildirim, A.; et al. The importance of the neutrophil-to-lymphocyte ratio in patients with hypertrophic cardiomyopathy. Rev. Port. Cardiol. 2017, 36, 239–246. [Google Scholar] [CrossRef]
- Kaya, H.; Ertas, F.; Soydinc, M.S. Association between neutrophil to lymphocyte ratio and severity of coronary artery disease. Clin. Appl. Thromb. Hemost. 2014, 20, 221. [Google Scholar] [CrossRef] [Green Version]
- Adamstein, N.H.; MacFadyen, J.G.; Rose, L.M.; Glynn, R.J.; Dey, A.K.; Libby, P.; Tabas, I.A.; Mehta, N.N.; Ridker, P.M. The neutrophil–lymphocyte ratio and incident atherosclerotic events: Analyses from five contemporary randomized trials. Eur. Heart J. 2021, 42, 896–903. [Google Scholar] [CrossRef]
- Nowak, K.L.; Rossman, M.J.; Chonchol, M.; Seals, D.R. Strategies for Achieving Healthy Vascular Ageing. Hypertension 2018, 71, 389–402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cicero, A.F.G.; Toth, P.P.; Fogacci, F.; Virdis, A.; Borghi, C. Improvement in arterial stiffness after short-term treatment with PCSK9 inhibitors. Nutr. Metab. Cardiovasc. Dis. 2019, 29, 527–529. [Google Scholar] [CrossRef] [PubMed]
- Picker, S.M. Antiplatelet therapy in the prevention of coronary syndromes: Mode of action, benefits, drawbacks. Cardiovasc. Hematol. Agents Med. Chem. 2013, 11, 49–57. [Google Scholar] [CrossRef] [PubMed]
- Berger, J.S.; Brown, D.L.; Becker, R.C. Low-dose aspirin in patients with stable cardiovascular disease: A meta-analysis. Am. J. Med. 2008, 121, 43–49. [Google Scholar] [CrossRef] [PubMed]
- Hennekens, C.H. Aspirin in the treatment and prevention of cardiovascular disease: Current perspectives and future directions. Curr. Atheroscler. Rep. 2007, 9, 409–416. [Google Scholar] [CrossRef] [PubMed]
- Gaziano, J.M.; Brotons, C.; Coppolecchia, R.; Cricelli, C.; Darius, H.; Gorelick, P.B.; Howard, G.; Pearson, T.A.; Rothwell, P.M.; Ruilope, L.M.; et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): A randomised, double-blind, placebo-controlled trial. Lancet 2018, 392, 1036–1046. [Google Scholar] [CrossRef]
- McNeil, J.J.; Woods, R.L.; Nelson, M.R.; Reid, C.M.; Kirpach, B.; Wolfe, R.; Storey, E.; Shah, R.C.; Lockery, J.E.; Tonkin, A.M.; et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N. Engl. J. Med. 2018, 379, 1499–1508. [Google Scholar] [CrossRef]
- Group, A.S.C.; Bowman, L.; Mafham, M.; Wallendszus, K.; Stevens, W.; Buck, G.; Barton, J.; Murphy, K.; Aung, T.; Haynes, R.; et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N. Engl. J. Med. 2018, 379, 1529–1539. [Google Scholar] [CrossRef]
- Piepoli, M.F.; Hoes, A.W.; Agewall, S.; Albus, C.; Brotons, C.; Catapano, A.L.; Cooney, M.T.; Corra, U.; Cosyns, B.; Deaton, C.; et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur. Heart J. 2016, 37, 2315–2381. [Google Scholar] [CrossRef] [PubMed]
- Ferruzzi, J.; Collins, M.J.; Yeh, A.T.; Humphrey, J.D. Mechanical assessment of elastin integrity in fibrillin-1-deficient carotid arteries: Implications for Marfan syndrome. Cardiovasc. Res. 2011, 92, 287–295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Medley, T.L.; Cole, T.J.; Gatzka, C.D.; Wang, W.Y.; Dart, A.M.; Kingwell, B.A. Fibrillin-1 genotype is associated with aortic stiffness and disease severity in patients with coronary artery disease. Circulation 2002, 105, 810–815. [Google Scholar] [CrossRef] [Green Version]
- Mariko, B.; Pezet, M.; Escoubet, B.; Bouillot, S.; Andrieu, J.P.; Starcher, B.; Quaglino, D.; Jacob, M.P.; Huber, P.; Ramirez, F.; et al. Fibrillin-1 genetic deficiency leads to pathological ageing of arteries in mice. J. Pathol. 2011, 224, 33–44. [Google Scholar] [CrossRef] [Green Version]
- Sherratt, M.J. Tissue elasticity and the ageing elastic fibre. Age 2009, 31, 305–325. [Google Scholar] [CrossRef] [Green Version]
- Tsamis, A.; Krawiec, J.T.; Vorp, D.A. Elastin and collagen fibre microstructure of the human aorta in ageing and disease: A review. J. R. Soc. Interface 2013, 10, 20121004. [Google Scholar] [CrossRef]
- Van der Donckt, C.; Van Herck, J.L.; Schrijvers, D.M.; Vanhoutte, G.; Verhoye, M.; Blockx, I.; Van Der Linden, A.; Bauters, D.; Lijnen, H.R.; Sluimer, J.C.; et al. Elastin fragmentation in atherosclerotic mice leads to intraplaque neovascularization, plaque rupture, myocardial infarction, stroke, and sudden death. Eur. Heart J. 2015, 36, 1049–1058. [Google Scholar] [CrossRef] [Green Version]
- Van Herck, J.L.; De Meyer, G.R.Y.; Martinet, W.; Van Hove, C.E.; Foubert, K.; Theunis, M.H.; Apers, S.; Bult, H.; Vrints, C.J.; Herman, A.G. Impaired Fibrillin-1 Function Promotes Features of Plaque Instability in Apolipoprotein E-Deficient Mice. Circulation 2009, 120, 2478–2487. [Google Scholar] [CrossRef] [Green Version]
- Emini Veseli, B.; Perrotta, P.; De Meyer, G.R.A.; Roth, L.; Van der Donckt, C.; Martinet, W.; De Meyer, G.R.Y. Animal models of atherosclerosis. Eur. J. Pharmacol. 2017, 816, 3–13. [Google Scholar] [CrossRef]
- Judge, D.P.; Biery, N.J.; Keene, D.R.; Geubtner, J.; Myers, L.; Huso, D.L.; Sakai, L.Y.; Dietz, H.C. Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome. J. Clin. Investig. 2004, 114, 172–181. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hickman, D.L. Evaluation of the neutrophil:lymphocyte ratio as an indicator of chronic distress in the laboratory mouse. Lab. Anim. 2017, 46, 303–307. [Google Scholar] [CrossRef] [Green Version]
- Mayyas, F.A.; Al-Jarrah, M.I.; Ibrahim, K.S.; Alzoubi, K.H. Level and significance of plasma myeloperoxidase and the neutrophil to lymphocyte ratio in patients with coronary artery disease. Exp. Ther. Med. 2014, 8, 1951–1957. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O. Neutrophils in atherosclerosis. A brief overview. Hamostaseologie 2015, 35, 121–127. [Google Scholar] [CrossRef]
- Silvestre-Roig, C.; Braster, Q.; Ortega-Gomez, A.; Soehnlein, O. Neutrophils as regulators of cardiovascular inflammation. Nat. Rev. Cardiol. 2020, 17, 327–340. [Google Scholar] [CrossRef]
- Santos, H.O.; Izidoro, L.F.M. Neutrophil–lymphocyte Ratio in Cardiovascular Disease Risk Assessment. Int. J. Cardiovasc. Sci. 2018, 31, 532–537. [Google Scholar] [CrossRef]
- Kaartinen, V.; Warburton, D. Fibrillin controls TGF-beta activation. Nat. Genet. 2003, 33, 331–332. [Google Scholar] [CrossRef]
- Buday, A.; Orsy, P.; Godo, M.; Mozes, M.; Kokeny, G.; Lacza, Z.; Koller, A.; Ungvari, Z.; Gross, M.L.; Benyo, Z.; et al. Elevated systemic TGF-beta impairs aortic vasomotor function through activation of NADPH oxidase-driven superoxide production and leads to hypertension, myocardial remodeling, and increased plaque formation in apoE(-/-) mice. Am. J. Physiol. Heart Circ. Physiol. 2010, 299, H386–H395. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nataatmadja, M.; West, J.; West, M. Overexpression of transforming growth factor-beta is associated with increased hyaluronan content and impairment of repair in Marfan syndrome aortic aneurysm. Circulation 2006, 114, I371–I377. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pietri, P.; Vlachopoulos, C.; Terentes-Printzios, D.; Xaplanteris, P.; Aznaouridis, K.; Petrocheilou, K.; Stefanadis, C. Beneficial effects of low-dose aspirin on aortic stiffness in hypertensive patients. Vasc. Med. 2014, 19, 452–457. [Google Scholar] [CrossRef] [Green Version]
- Lee, S.H.; Pekas, E.J.; Lee, S.; Headid, R.J., 3rd; Park, S.Y. The Impact of Aspirin Intake on Lactate Dehydrogenase, Arterial Stiffness, and Oxidative Stress During High-Intensity Exercise: A Pilot Study. J. Hum. Kinet. 2020, 72, 101–113. [Google Scholar] [CrossRef] [Green Version]
- Franken, R.; Hibender, S.; den Hartog, A.W.; Radonic, T.; de Vries, C.J.; Zwinderman, A.H.; Groenink, M.; Mulder, B.J.; de Waard, V. No beneficial effect of general and specific anti-inflammatory therapies on aortic dilatation in Marfan mice. PLoS ONE 2014, 9, e107221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, X.; Lu, J.; Khaidakov, M.; Mitra, S.; Ding, Z.; Raina, S.; Goyal, T.; Mehta, J.L. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription. Toxicol. Appl. Pharmacol. 2012, 259, 346–354. [Google Scholar] [CrossRef] [PubMed]
- Mulay, S.R.; Gaikwad, A.B.; Tikoo, K. Combination of aspirin with telmisartan suppresses the augmented TGFbeta/smad signalling during the development of streptozotocin-induced type I diabetic nephropathy. Chem. Biol. Interact. 2010, 185, 137–142. [Google Scholar] [CrossRef] [PubMed]
- Humphrey, J.D.; Harrison, D.G.; Figueroa, C.A.; Lacolley, P.; Laurent, S. Central Artery Stiffness in Hypertension and Ageing: A Problem With Cause and Consequence. Circ. Res. 2016, 118, 379–381. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Guo, H.; Xu, D.; Xu, X.; Wang, H.; Hu, X.; Lu, Z.; Kwak, D.; Xu, Y.; Gunther, R.; et al. Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: Heart failure causes severe lung disease. Hypertension 2012, 59, 1170–1178. [Google Scholar] [CrossRef]
- Ismahil, M.A.; Hamid, T.; Bansal, S.S.; Patel, B.; Kingery, J.R.; Prabhu, S.D. Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: Critical importance of the cardiosplenic axis. Circ. Res. 2014, 114, 266–282. [Google Scholar] [CrossRef] [Green Version]
- Prabhu, S.D. The Cardiosplenic Axis Is Essential for the Pathogenesis of Ischemic Heart Failure. Trans. Am. Clin. Climatol. Assoc. 2018, 129, 202–214. [Google Scholar]
- Jackson, C.L.; Bennett, M.R.; Biessen, E.A.L.; Johnson, J.L.; Krams, R. Assessment of unstable atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 714–720. [Google Scholar] [CrossRef] [Green Version]
ApoE−/− | ApoE−/−Fbn1C1039G+/− | Main Effect p Values | |||||
---|---|---|---|---|---|---|---|
Control | ASA | Control | ASA | G | T | I | |
Mortality (%) 1 | 0 (0/15) | 0 (0/14) | 52 (11/21) | 58 (11/19) | 1 × 10−6 | 0.805 | / |
Cholesterol (mg/dL) 2 | 440 ± 26 | 414 ± 24 | 488 ± 40 | 423 ± 25 | 0.359 | 0.146 | 0.537 |
Body weight (g) 2 | 23.3 ± 0.7 | 22.5 ± 0.7 | 20.5 ± 0.7 § | 19.5 ± 0.9 | 0.001 | 0.244 | 0.870 |
Heart weight/BW (%) 2 | 0.50 ± 0.02 | 0.49 ± 0.02 | 1.16 ± 0.12 §§§ | 0.76 ± 0.05 *** | 3 × 10−13 | 0.002 | 0.004 |
Lung weight/BW (%) 2 | 0.69 ± 0.03 | 0.68 ± 0.02 | 0.99 ± 0.09 §§§ | 0.87 ± 0.04 | 4 × 10−6 | 0.280 | 0.431 |
Spleen weight/BW (%) 2 | 0.48 ± 0.03 | 0.40 ± 0.02 | 0.81 ± 0.10 §§§ | 0.58 ± 0.07 * | 2 × 10−5 | 0.004 | 0.341 |
ApoE−/− | ApoE−/−Fbn1C1039G+/− | Main Effect p Values | |||||
---|---|---|---|---|---|---|---|
Control | ASA | Control | ASA | G | T | I | |
Dendritic cells (cells/µL) | 130 ± 26 | 99 ± 25 | 78 ± 23 | 76 ± 18 | 0.161 | 0.537 | 0.587 |
Ly-6Chi monocytes (cells/µL) | 397 ± 48 | 391 ± 50 | 686 ± 111 §§ | 521 ± 54 | 0.004 | 0.219 | 0.254 |
Ly-6Clo monocytes (cells/µL) | 451 ± 55 | 440 ± 78 | 499 ± 84 | 536 ± 74 | 0.341 | 0.859 | 0.744 |
T cells (cells/µL) | 1095 ± 152 | 1129 ± 272 | 879 ± 160 | 1325 ± 243 | 0.965 | 0.281 | 0.354 |
B cells (cells/µL) | 2044 ± 240 | 2480 ± 488 | 2157 ± 562 | 3201 ± 635 | 0.379 | 0.122 | 0.520 |
NK cells (cells/µL) | 463 ± 48 | 426 ± 67 | 539 ± 73 | 466 ± 101 | 0.414 | 0.440 | 0.796 |
NKT cells (cells/µL) | 63 ± 12 | 81 ± 24 | 64 ± 12 | 68 ± 10 | 0.724 | 0.516 | 0.694 |
ApoE−/− | ApoE−/−Fbn1C1039G+/− | Main Effect p Values | ||||||
---|---|---|---|---|---|---|---|---|
Control | ASA | Control | ASA | G | T | I | ||
Proximal ascending aorta | Plaque size (103 µm2) 1 | 522 ± 47 | 467 ± 28 | 1255 ± 135 §§§ | 1229 ± 153 | 1 × 10−8 | 0.578 | 0.818 |
Stenosis (%) 1 | 46.6 ± 3.2 | 44.4 ± 1.9 | 60.3 ± 1.5 §§ | 58.0 ± 3.4 | 4 × 10−5 | 0.444 | 0.979 | |
IEL length (µm) 1 | 3740 ± 93 | 3558 ± 57 | 4776 ± 259 §§ | 5063 ± 288 | 3 × 10−6 | 0.988 | 0.347 | |
Necrotic core (%) 1 | 15.1 ± 2.3 | 11.8 ± 2.7 | 18.2 ± 2.1 | 19.6 ± 3.7 | 0.082 | 0.765 | 0.452 | |
SMCs (%) 1 | 5.6 ± 0.8 | 6.4 ± 1.0 | 4.9 ± 0.6 | 4.9 ± 0.6 | 0.130 | 0.575 | 0.558 | |
Cap thickness (µm) 1 | 12.1 ± 3.1 | 9.9 ± 1.8 | 9.1 ± 1.0 | 12.5 ± 1.4 | 0.907 | 0.713 | 0.125 | |
Total collagen (%) 1 | 67.9 ± 2.2 | 68.7 ± 1.8 | 64.5 ± 2.1 | 61.2 ± 2.2 | 0.020 | 0.588 | 0.370 | |
Glycosaminoglycans (%) 1 | 51.2 ± 2.0 | 56.0 ± 2.4 | 50.4 ± 2.9 | 53.3 ± 2.0 | 0.501 | 0.148 | 0.717 | |
p-SMAD2/3 positive nuclei (%) 1 | 67.5 ± 5.6 | 68.1 ± 1.4 | 67.8 ± 3.5 | 58.5 ± 3.3 | 0.443 | 0.796 | 0.588 | |
Leukocytes (%) 1 | 6.0 ± 0.6 | 7.1 ± 0.6 | 6.7 ± 0.5 | 8.1 ± 0.8 | 0.204 | 0.080 | 0.819 | |
Macrophages (%) 1 | 4.1 ± 0.6 | 3.8 ± 0.4 | 3.5 ± 0.4 | 2.9 ± 0.4 | 0.114 | 0.260 | 0.732 | |
Carotid artery | Plaque formation index (%) 1 | 55 ± 6 | 61 ± 7 | 83 ± 3 §§ | 79 ± 4 | 1 × 10−4 | 0.844 | 0.364 |
IP microvessel occurrence (%) 2 | 8 | 25 | 36 | 46 | 0.060 | 0.311 | / | |
IP bleeding occurrence (%) 2 | 8 | 25 | 29 | 38 | 0.173 | 0.296 | / | |
Coronary arteries—MI | Plaque occurrence (%) 2 | 47 | 43 | 44 | 47 | 0.979 | 0.979 | / |
Plaque size (µm2) 1 | 9515 ± 4706 | 7616 ± 2417 | 4043 ± 516 | 5518 ± 2378 | 0.222 | 0.944 | 0.581 | |
Stenosis (%) 1 | 50 ± 17 | 69 ± 13 | 47 ± 7 | 37 ± 8 | 0.158 | 0.699 | 0.237 | |
MI occurrence (%) 2 | 13 | 14 | 38 | 40 | 0.029 | 0.876 | / |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Roth, L.; Rombouts, M.; Schrijvers, D.M.; Emini Veseli, B.; Martinet, W.; De Meyer, G.R.Y. Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis. Int. J. Mol. Sci. 2022, 23, 404. https://doi.org/10.3390/ijms23010404
Roth L, Rombouts M, Schrijvers DM, Emini Veseli B, Martinet W, De Meyer GRY. Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis. International Journal of Molecular Sciences. 2022; 23(1):404. https://doi.org/10.3390/ijms23010404
Chicago/Turabian StyleRoth, Lynn, Miche Rombouts, Dorien M. Schrijvers, Besa Emini Veseli, Wim Martinet, and Guido R. Y. De Meyer. 2022. "Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis" International Journal of Molecular Sciences 23, no. 1: 404. https://doi.org/10.3390/ijms23010404
APA StyleRoth, L., Rombouts, M., Schrijvers, D. M., Emini Veseli, B., Martinet, W., & De Meyer, G. R. Y. (2022). Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis. International Journal of Molecular Sciences, 23(1), 404. https://doi.org/10.3390/ijms23010404