ArticleInternational journal of molecular sciences2021
Elucidating Carfilzomib's Induced Cardiotoxicity in an In Vivo Model of Aging: Prophylactic Potential of Metformin.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Review
- Cardiotoxicity induced by multiple myeloma therapies: mechanistic convergence across proteasome inhibitors, CAR-T, and bispecific antibodies.Blood cancer journal · 2026Review
- Article
- Cardiotoxicity Induced by Anticancer Therapies: A Call for Integrated Cardio-Oncology Practice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Carfilzomib in multiple myeloma: unraveling cardiac toxicities - from mechanisms to diagnosis and management.Frontiers in pharmacology · 2025Review
- Article
- Empagliflozin Alleviates Carfilzomib-Induced Cardiotoxicity in Mice by Modulating Oxidative Stress, Inflammatory Response, Endoplasmic Reticulum Stress, and Autophagy.Antioxidants (Basel, Switzerland) · 2024Article
- Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension-Mechanisms and Mitigation.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Article
- An Untargeted Metabolomics Approach on Carfilzomib-Induced Nephrotoxicity.Molecules (Basel, Switzerland) · 2022Article
- Mineralocorticoid Receptor Pathway Is a Key Mediator of Carfilzomib-induced Nephrotoxicity: Preventive Role of Eplerenone.HemaSphere · 2022Article
- Metformin Induces Resistance of Cancer Cells to the Proteasome Inhibitor Bortezomib.Biomolecules · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCarfilzomib is a first-line proteasome inhibitor indicated for relapsed/refractory multiple myeloma (MM), with its clinical use being hampered by cardiotoxic phenomena. We have previously established a translational model of carfilzomib cardiotoxicity in young adult mice, in which metformin emerged as a prophylactic therapy. Considering that MM is an elderly disease and that age is an independent risk factor for cardiotoxicity, herein, we sought to validate carfilzomib's cardiotoxicity in an in vivo model of aging.
methodsAged mice underwent the translational two- and four-dose protocols without and with metformin. Mice underwent echocardiography and were subsequently sacrificed for molecular analyses in the blood and cardiac tissue.
resultsCarfilzomib decreased proteasomal activity both in PBMCs and myocardium in both protocols. Carfilzomib induced mild cardiotoxicity after two doses and more pronounced cardiomyopathy in the four-dose protocol, while metformin maintained cardiac function. Carfilzomib led to an increased Bip expression and decreased AMPKα phosphorylation, while metformin coadministration partially decreased Bip expression and induced AMPKα phosphorylation, leading to enhanced myocardial LC3B-dependent autophagy.
conclusionCarfilzomib induced cardiotoxicity in aged mice, an effect significantly reversed by metformin. The latter possesses translational importance as it further supports the clinical use of metformin as a potent prophylactic therapy.
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