Hemosiderin Accumulation in Liver Decreases Iron Availability in Tachycardia-Induced Porcine Congestive Heart Failure Model

Abstract

Despite advances in the management of iron deficiency in heart failure (HF), the mechanisms underlying the effects of treatment remain to be established. Iron distribution and metabolism in HF pathogenesis need to be clarified. We used a porcine tachycardia-induced cardiomyopathy model to find out how HF development influences hepatic and myocardial iron storing, focusing on ferritin, the main iron storage protein. We found that cumulative liver congestion (due to the decrease of heart function) overwhelms its capacity to recycle iron from erythrocytes. As a consequence, iron is trapped in the liver as poorly mobilized hemosiderin. What is more, the ferritin-bound Fe3+ (reflecting bioavailable iron stores), and assembled ferritin (reflecting ability to store iron) are decreased in HF progression in the liver. We demonstrate that while HF pigs show iron deficiency indices, erythropoiesis is enhanced. Renin–angiotensin–aldosterone system activation and hepatic hepcidin suppression might indicate stress erythropoiesisinduced in HF. Furthermore, assembled ferritin increases but ferritin-bound Fe3+ is reduced in myocardium, indicating that a failing heart increases the iron storage reserve but iron deficiency leads to a drop in myocardial iron stores. Together, HF in pigs leads to down-regulated iron bioavailability and reduced hepatic iron storage making iron unavailable for systemic/cardiac needs.

A Single Infusion of Polyethylene Glycol-Coated Superparamagnetic Magnetite Nanoparticles Alters Differently the Expressions of Genes Involved in Iron Metabolism in the Liver and Heart of Rats

“…Thus, our data showed considerable differences in the expression of genes involved in iron metabolism in the heart and the liver of rats. In agreement, a recent study by Kasztura et al [ 63 ] has shown that the mechanisms of iron uptake, storage and clearance differ between the liver and heart in the porcine model of heart failure progression.…”

Iron parameters analysis in dogs with myxomatous mitral valve disease

“…Hence, the iron balance in various human disease stages and safe iron supplementation in different clinical conditions are being studied with increasing attention. It has been observed that in physiological conditions, iron is not excreted from the body, and any iron excess is stored in safe cell deposits in the form of ferritin, distributed mainly in the liver macrophages, spleen, and other organs and cells [ 7 ]. In the presented study, Western blotting showed the presence of good quality bands for ferritin and soluble transferrin receptor, which did not differ between the studied groups.…”

“…However, since the prognosis and survival of HF patients with ID (with or without anemia) are worse compared to HF patients without ID, the European Society of Cardiology (ESC) recommends supplementing iron intravenously, e.g., with ferric carboxymaltose, in HF patients with ID [ 13 , 18 ]. Iron deficiency has been reported in animals (pigs and rodents) with experimentally induced HF [ 7 , 24 ]. However, only a few studies on iron management in HF dogs are available [ 22 , 25 ], despite HF being a common disease of older and small breed dogs, especially Cavalier King Charles Spaniel (CKCS), dachshund, miniature poodle, Maltese, Chihuahua, Pomeranian, or Yorkshire terriers [ 1 ].…”

“…The high prevalence of iron deficiency (ID) in humans and other species (e.g., rats, mice, and pigs) with heart failure (HF) and its association with worse prognosis make iron deficiency an interesting target in dogs with MMVD. In murine and porcine animal models of HF, ID is associated with exercise intolerance, worsened quality of life, and cardiac remodelling [ 5 – 7 ]. Early indices of anemia, visible as an increased percentage of poikilocytes in the erythrocytes population during detailed assessment of the size and shape changes of red blood cells in blood smear were observed in dogs with MMVD [ 8 ].…”

Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy

“… 82 FTH1 exhibits iron oxidase activity, converting excess Fe 2+ to Fe 3+ , while FTL allows for Fe 3+ storage. 83 Fe 2+ is mainly excreted from the cell membrane by the solute carrier family 40 member 1 (SLC40A1) or can be expelled as Ferritin via exosomes. 84 The protein prominin 2 promotes the formation of polyvesicles and exosomes, facilitating iron excretion from cells and maintaining the dynamic equilibrium of intracellular iron levels.…”