{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:35Z","timestamp":1760146235412,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 Research and Innovation Program","award":["No858070","BOF-DOCPRO1"],"award-info":[{"award-number":["No858070","BOF-DOCPRO1"]}]},{"name":"Research Council of the University of Antwerp","award":["No858070","BOF-DOCPRO1"],"award-info":[{"award-number":["No858070","BOF-DOCPRO1"]}]},{"name":"Scientific Research (FWO)-Flanders","award":["No858070","BOF-DOCPRO1"],"award-info":[{"award-number":["No858070","BOF-DOCPRO1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Proteasome inhibitors such as bortezomib and carfilzomib induce apoptosis and are a cornerstone in the treatment of relapsed or refractory multiple myeloma. However, concerns have emerged concerning their link to cancer therapy-related cardiovascular dysfunction (CTRCD). Bortezomib, a reversible first-generation inhibitor, and carfilzomib, a second-generation irreversible inhibitor, are associated with hypertension, heart failure, and cardiac arrhythmias. The current study investigated the effects of bortezomib and carfilzomib on cardiac (left ventricular ejection fraction, LVEF) and vascular (arterial stiffness, vascular reactivity) function. Cardiac function assessment aimed to build upon existing evidence of proteasome inhibitors CTRCD, while arterial stiffness served as an early indicator of potential vascular remodeling. Groups of 12-week-old C57BL\/6J male mice (n = 8 per group) were randomly assigned to receive vehicle, carfilzomib (8 mg\/kg I.P.), or bortezomib (0.5 mg\/kg I.P.). Additionally, proteasome inhibition was assessed in mice treated with L-NAME (0.5 mg\/kg) to induce hypertension. Cardiac and vascular parameters were evaluated via echocardiography on days 0 and 3. On day 6, mice were sacrificed for ex vivo analysis of arterial stiffness and vascular reactivity. Overall, no changes in arterial stiffness were detected either in vivo or ex vivo at basal pressures. However, a steeper pressure\u2013stiffness curve was observed for carfilzomib in normotensive (p &lt; 0.01) and hypertensive (p &lt; 0.0001) mice ex vivo. Additionally, in hypertensive mice, carfilzomib decreased LVEF (p = 0.06), with bortezomib exhibiting similar trends. Vascular reactivity remained largely unchanged, but proteasome inhibition tended to enhance endothelial-independent relaxations in both control and hypertensive mice. In conclusion, short-term treatment with carfilzomib and bortezomib is considered relatively safe for the protocols assessed in the study.<\/jats:p>","DOI":"10.3390\/biology13100844","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T10:49:22Z","timestamp":1729507762000},"page":"844","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Short-Term Proteasome Inhibition: Assessment of the Effects of Carfilzomib and Bortezomib on Cardiac Function, Arterial Stiffness, and Vascular Reactivity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2213-4426","authenticated-orcid":false,"given":"Callan D.","family":"Wesley","sequence":"first","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5175-040X","authenticated-orcid":false,"given":"Annarita","family":"Sansonetti","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7074-226X","authenticated-orcid":false,"given":"Cedric H. G.","family":"Neutel","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin N.","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3848-8702","authenticated-orcid":false,"given":"Guido R. Y.","family":"De Meyer","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-9343","authenticated-orcid":false,"given":"Wim","family":"Martinet","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8640-6620","authenticated-orcid":false,"given":"Pieter-Jan","family":"Guns","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"ref_1","first-page":"2615","article-title":"Proteasome inhibitors: A novel class of potent and effective antitumor agents","volume":"59","author":"Adams","year":"1999","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrm1552","article-title":"Proteolysis: From the lysosome to ubiquitin and the proteasome","volume":"6","author":"Ciechanover","year":"2005","journal-title":"Nat. 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