Abstract 17165: Myocardial Iron Depletion In Patients With Heart Failure Is Associated With Mitochondrial Dysfunction And Attenuation Of Citrate Synthase Activity
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Medientyp:
E-Artikel
Titel:
Abstract 17165: Myocardial Iron Depletion In Patients With Heart Failure Is Associated With Mitochondrial Dysfunction And Attenuation Of Citrate Synthase Activity
Beschreibung:
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<jats:bold>Introduction:</jats:bold>
Very little is known about the determinants and consequences of abnormal iron (Fe) content in the failing human myocardium.
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<jats:bold>Hypothesis:</jats:bold>
We hypothesized that myocardial Fe deficiency (ID) in heart failure (HF) is associated with impaired mitochondrial function of Fe-regulated enzymes of respiratory chain (RC) and Krebs (TCA) cycle.
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<jats:bold>Methods:</jats:bold>
LV samples were obtained from 90 consecutive patients undergoing transplantation (HF: LVEF 23±8%, age 53±11y, 83% males, 46% CAD, 24 % diabetes) and from 38 HF-free organ donors (CON: LVEF 57±12%, age 42±15y, 50% males, 14% with diabetes). Activities of citrate synthase (CS, Krebs cycle) and RC enzymes NADH-cytochrome c oxidoreductase (NCCR), succinate cytochrome c oxidoreductase (SCCR) and cytochrome c oxidase (COX) were measured in homogenates. Total Fe was measured by ICP-MS after microwave-assisted digestion of lyophilized samples.
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<jats:bold>Results:</jats:bold>
Compared to CON, HF patients had lower total myocardial Fe (156±41 vs 200±38 μg/g dry weight, p<0.001). Myocardial ID (Fe<124.8 μg/g; 2*SD from the mean of CON) was present in 22 % of HF patients. HF+ID patients had more often diabetes (45% vs 18%, p=0.02), but similar age, gender, renal function, haemoglobin concentration, HF aetiology, LVEF or BNP as non-ID HF. Activities of CS, COX, SCCR and NCCR were all reduced in HF vs. CON (-21%, -34%, -28% and -26%, all p<0.001). In HF, Fe correlated with CS (r=0.30, p=0.004) and SCCR activities (r=0.24, p=0.02), but not with COX or NCCR. In pooled cohort, Fe also displayed strongest relation with CS (figure). HF+ID patients displayed reduced CS activity (516±145 vs 613±19, p=0.03), in contrast to preserved RC enzymes.
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<jats:bold>Conclusions:</jats:bold>
Myocardial Fe content is systematically diminished in advanced HF and is associated with mitochondrial dysfunction, in particular with reduced CS activity. These relations may reflect Fe-dependent regulation of aconitase (TCA cycle enzyme) and may influence the utilization of energetic substrates.
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