An iron-deficient diet in rats induced adaptive cardiac hypertrophy with increased STAT3 and VEGF by 12 weeks, which transitioned to cardiac fibrosis and lung congestion after 20 weeks.
Long-term iron deficiency anemia in a rat model induces an initial adaptive cardiac hypertrophy mediated by Epo and STAT3 that eventually transitions to maladaptive cardiac fibrosis and dysfunction.
Anemia is common in patients with chronic heart failure and an independent predictor of poor prognosis. Chronic anemia leads to left ventricular (LV) hypertrophy and heart failure, but its molecular mechanisms remain largely unknown. We investigated the mechanisms, including the molecular signaling pathway, of cardiac remodeling induced by iron deficiency anemia (IDA). Weanling Sprague-Dawley rats were fed an iron-deficient diet for 20 wk to induce IDA, and the molecular mechanisms of cardiac remodeling were evaluated. The iron-deficient diet initially induced severe anemia, which resulted in LV hypertrophy and dilation with preserved systolic function associated with increased serum erythropoietin (Epo) concentration. Cardiac STAT3 phosphorylation and VEGF gene expression increased by 12 wk of IDA, causing angiogenesis in the heart. Thereafter, sustained IDA induced upregulation of cardiac hypoxia inducible factor-1alpha gene expression and maintained upregulation of cardiac VEGF gene expression and cardiac angiogenesis; however, sustained IDA promoted cardiac fibrosis and lung congestion, with decreased serum Epo concentration and cardiac STAT3 phosphorylation after 20 wk of IDA compared with 12 wk. Upregulation of serum Epo concentration and cardiac STAT3 phosphorylation is associated with a beneficial adaptive mechanism of anemia-induced cardiac hypertrophy, and later decreased levels of these molecules may be critical for the transition from adaptive cardiac hypertrophy to cardiac dysfunction in long-term anemia. Understanding the mechanism of cardiac maladaptation to anemia may lead to a new strategy for treatment of chronic heart failure with anemia.
Naito et al. (Sat,) conducted a other in Iron deficiency anemia. Iron-deficient diet was evaluated on Cardiac remodeling and molecular signaling pathways. An iron-deficient diet in rats induced adaptive cardiac hypertrophy with increased STAT3 and VEGF by 12 weeks, which transitioned to cardiac fibrosis and lung congestion after 20 weeks.
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