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Carfilzomib (Cfz), indicated for relapsed\/refractory multiple myeloma (MM), presents with serious CAEs. MM is often accompanied with co\u2010existing comorbidities. However, Cfz use in MM patients with cardiometabolic syndrome (CMS) or in heart failure with reduced ejection fraction (HFrEF), is questionable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and C57BL6\/J male mice received 14\u2009weeks Western Diet (WD) (CMS models). C57BL6\/J male mice underwent permanent LAD ligation for 14\u2009days (early\u2010stage HFrEF model). CMS\u2010 and HFrEF\u2010burdened mice received Cfz for two consecutive or six alternate days. Daily metformin and atorvastatin administrations were performed additionally to Cfz, as prophylactic interventions. Mice underwent echocardiography, while proteasome activity, biochemical and molecular analyses were conducted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      CMS did not exacerbate Cfz left ventricular (LV) dysfunction, whereas Cfz led to metabolic complications in both CMS models. Cfz induced autophagy and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      homeostasis dysregulation, whereas metformin and atorvastatin prevented Cfz\u2010mediated LV dysfunction and molecular deficits in the CMS\u2010burdened myocardium. Early\u2010stage HFrEF led to depressed LV function and increased protein phosphatase 2A (PP2A) activity. Cfz further increased myocardial PP2A activity, inflammation and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010cycling dysregulation. Metformin co\u2010administration exerted an anti\u2010inflammatory potential on the myocardium without improving LV function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      CMS and HFrEF seem to exacerbate Cfz\u2010induced CAEs, by presenting metabolism\u2010related hidden toxicity and PP2A\u2010related cardiac inflammation, respectively. Metformin retains its prophylactic potential in the presence of CMS, while mitigating inflammation and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signalling dysregulation in the HFrEF myocardium.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16391","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T02:19:31Z","timestamp":1714357171000},"page":"2964-2990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["RETRACTED: Implications and hidden toxicity of cardiometabolic syndrome and early\u2010stage heart failure in carfilzomib\u2010induced cardiotoxicity"],"prefix":"10.1111","volume":"181","author":[{"given":"Panagiotis","family":"Efentakis","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimilia","family":"Varela","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation of the Academy of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Lamprou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni\u2010Dimitra","family":"Papanagnou","sequence":"additional","affiliation":[{"name":"Department of Biology National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Chatzistefanou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriana","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos H.","family":"Davos","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation of the Academy of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gavriatopoulou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Plasma Cell Dyscrasias Unit National and Kapodistrian University of Athens, Medical School  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Trougakos","sequence":"additional","affiliation":[{"name":"Department of Biology National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meletios Athanasios","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Plasma Cell Dyscrasias Unit National and Kapodistrian University of Athens, Medical School  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Terpos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Plasma Cell Dyscrasias Unit National and Kapodistrian University of Athens, Medical School  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Andreadou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.315937"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415617"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16182"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16176"},{"key":"e_1_2_13_10_1","doi-asserted-by":"crossref","unstructured":"Andreadou I Schulz R Badimon L Adameov\u00e1 A Kleinbongard P Lecour S Nikolaou PE Falc\u00e3o\u2010Pires I Vilahur G Woudberg N Heusch G Ferdinandy P. 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