Amlodipine rescues advanced iron overload cardiomyopathy in hemojuvelin knockout murine model: Clinical implications

• DOI: 10.3389/fcvm.2023.1129349
• Publication Date: 2023-04-21T04:28:44Z
• Authors: Pavel Zhabyeyev; Chandu Sadasivan; Saumya Shah; Faqi Wang; Gavin Y. Oudit
• Keywords: Amlodipine; Hereditary hemochromatosis; Ferroportin

Iron overload cardiomyopathy (IOC) is a major co-morbidity of genetic hemochromatosis and secondary iron with limited therapeutic options. We aim to investigate mechanisms rescue action amlodipine in the murine model overload, characterize changes human cardiac tissue due IOC, compare them animal IOC.As an model, we used male hemojuvelin knockout (HJVKO) mice, which lacked (a co-receptor protein for hepcidin expression). The mice were fed high-iron diet from 4 weeks 1 year age. As rescue, iron-fed received Ca2+ channel blocker, amlodipine, 9 12 months. resulted systolic diastolic dysfunctions similar explanted heart IOC. An IOC patient (β-thalassemia) left-ventricular ejection fraction (LVEF) 25% underwent transplantation. showed intra-myocyte deposition, fibrosis, hypertrophy, oxidative stress, remodeling cycling proteins, metabolic kinases typical failure. Single-myocyte contractility release diminished model. amlodipine-treated group exhibited normalization cellular function reversed remodeling. also report clinical case primary successfully treated amlodipine.The aged HJVKO on iron-rich reproduced many features use remodeling, demonstrating that effective adjuvant therapy