Iron deficiency without anemia is responsible for decreased left ventricular function and reduced mitochondrial complex I activity in a mouse model

Rineau, Emmanuel; Gaillard, Thomas; Guéguen, Naïg; Procaccio, Vincent; Henrion, Didier; Prunier, Fabrice; Lasocki, Sigismond

doi:10.1016/j.ijcard.2018.02.021

Cited by 38 publications

(42 citation statements)

References 26 publications

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“…Thus, to investigate the mechanism by which heterozygous deletion of TfR1 decreases angiogenesis in LI, we finally assessed mitochondrial complex in the ischemic adductor muscle. Of note, mitochondrial complex I expression in the ischemic adductor muscle was decreased in TfR1 +/− mice compared to WT mice, but not complexes II, III, and V. These results are consistent with a previous report in which iron deficiency without anemia impaired the expression cardiac mitochondrial complex I, but not the other complexes in mice 18 . Since the expression of all mitochondrial complexes in the adductor muscle did not differ significantly between WT and TfR1 +/− mice before the surgery, these results indicated that impaired mitochondrial complex I expression after the surgery depends on heterozygous TfR1 deletion in the ischemic adductor muscle.…”

Section: Discussionsupporting

confidence: 92%

Haploinsufficiency of Transferrin Receptor 1 Impairs Angiogenesis with Reduced Mitochondrial Complex I in Mice with Limb Ischemia

Okuno

Naito

Yasumura

et al. 2019

Sci Rep

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Limb ischemia (LI) is a major consequence of peripheral artery disease (PAD) with a high mortality rate. Iron is an essential mineral to maintain physiological function of multiple organs. Intracellular iron transport is regulated by transferrin receptor 1 (TfR1). Although increase in serum ferritin levels has been reported in PAD patients, the mechanism of iron metabolism in LI is still unclear. The aim of this study is to investigate whether TfR1 deletion attenuates LI formation. To generate LI, the left femoral artery of 8–10 week-old C57BL6/J male mice was ligated. Adductor muscles were harvested at 28 days after surgery to investigate iron metabolism. The level of ferritin, intracellular iron storage protein, was higher in ischemic adductor muscles compared to non-ischemic adductor muscles. Level of intracellular iron transport protein, TfR1, was decreased in ischemic adductor muscles. LI was then generated in TfR1 heterozygous deleted mice (TfR1+/−) to examine whether TfR1 contributes to the pathophysiology of LI. Laser Doppler blood flowmetry revealed that blood flow recovery was attenuated in TfR1+/− mice compared to wild type (WT) littermates, along with decreased expression of ferritin and CD31 in ischemic adductor muscles. Since iron is used for energy production in mitochondria, we then assessed mitochondrial complexes in the ischemic adductor muscle. Of interest, expression of mitochondrial complex I, but not complexes II, III, and V in ischemic adductor muscles was significantly reduced in TfR1+/− mice compared to WT mice. Haploinsufficiency of TfR1 attenuated angiogenesis via reduction of mitochondrial complex I in LI in mice.

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Section: Discussionsupporting

confidence: 92%

Haploinsufficiency of Transferrin Receptor 1 Impairs Angiogenesis with Reduced Mitochondrial Complex I in Mice with Limb Ischemia

Okuno

Naito

Yasumura

et al. 2019

Sci Rep

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“…This is also consistent with observations that ID is a risk factor for mortality and morbidity in patients with cardiac disease [ 4 ]. Indeed, ID has been shown to be responsible for decreased mitochondrial complex I activity, decreased exercise capacity and left ventricular ejection fraction in an animal model [ 31 ]. ID has been also associated with decreased muscular function (skeletal and myocardial) and this may explain the usual association reported between ID and fatigue [ 3 , 12 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Iron deficiency diagnosed using hepcidin on critical care discharge is an independent risk factor for death and poor quality of life at one year: an observational prospective study on 1161 patients

Lasocki¹,

Lefèbvre²,

Mayeur³

et al. 2018

Crit Care

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BackgroundIron deficiency is difficult to diagnose in critically ill patients, but may be frequent and may impair recovery. Measurement of hepcidin could help in the diagnosis of iron deficiency. We aim to assess if iron deficiency diagnosed using hepcidin is associated with poorer outcome one year after an intensive care unit stay.MethodsWe used the prospective FROG-ICU, multicentre (n = 28 ICUs), observational cohort study of critically ill survivors followed up one year after intensive care unit discharge. Iron deficiency was defined as hepcidin < 20 ng/l, ferritin < 100 ng/l or soluble transferrin receptor (sTfR)/log(ferritin) > 0.8, measured in blood drawn at intensive care unit discharge. Main outcomes were one-year all-cause mortality and poor quality of life (defined as a Short Form 36 (SF-36) score below the median).ResultsAmong the 2087 patients in the FROG-ICU cohort, 1570 were discharged alive and 1161 had a blood sample available at intensive care unit discharge and were included in the analysis. Using hepcidin, 429 (37%) patients had iron deficiency, compared to 72 (6%) using ferritin alone and 151 (13%) using the sTfR/log(ferritin) ratio. Iron deficiency diagnosed according to low hepcidin was an independent predictor of one-year mortality (OR 1.51 (1.10–2.08)) as was high sTfR/log ferritin ratio (OR = 1.95 (1.27–3.00)), but low ferritin was not. Severe ID, defined as hepcidin < 10 ng/l, was also an independent predictor of poor one-year physical recovery (1.58 (1.01–2.49)).ConclusionsIron deficiency, diagnosed using hepcidin, is very frequent at intensive care unit discharge and is associated with increased one-year mortality and poorer physical recovery. Whether iron treatment may improve these outcomes remains to be investigated.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2253-0) contains supplementary material, which is available to authorized users.

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“…Anemia in the older population is reported to be related to various medical burdens, including increased morbidity and mortality [7]. In particular, anemia is reported to be related to higher cardiovascular events [8,9], frailty [3,10,11], fractures [12], prolonged hospital stays, and unfavorable outcomes [13][14][15]. Robins et al showed that anemia in older population possesses potential morbidity and mortality by affecting tissue oxygen delivery, accompanying the aging process, and eventually leading to multiple major and minor organ dysfunction, affecting both physical and mental functions [16].…”

Section: Introductionmentioning

confidence: 99%

High anemia prevalence in Korean older adults, an advent healthcare problem: 2007–2016 KNHANES

et al. 2020

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Background Anemia is associated with high morbidity and mortality in older people. However, the prevalence and characteristics of anemia in older individuals are not fully understood, and national data on these aspects in older Korean adults are lacking. This study aimed to evaluate the prevalence and characteristics of anemia in older adults using data from the Korea National Health and Nutrition Examination Survey (KNHANES), which is a nationwide cross-sectional epidemiological study conducted by the Korean Ministry of Health and Welfare. Methods Data from a total of 62,825 participants of the 2007–2016 KNHANES were compiled and analyzed to investigate differences in participant characteristics and potential risk factors for anemia. Differences in clinical characteristics of participants were compared across subgroups using the chi-square test for categorical variables and independent t-test for continuous variables. Univariate and multivariate analyses using logistic regression were performed to identify related clinical factors. Results The prevalence of anemia was higher in the population aged ≥65 years than in the younger population. Anemia was also more prevalent among females than among males, but this difference was not significant in people aged > 85 years. Being underweight, receiving a social allowance, living alone, and having comorbidities such as hypertension, rheumatoid arthritis, diabetes mellitus (DM), cancer, and chronic renal failure (CRF) were more common among older adults with anemia than among the population without anemia. In univariate and multivariate analyses, older age, female sex, underweight, and presence of comorbidities including rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia. Conclusions This study revealed that age, female sex, underweight, and the presence of comorbidities such as rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia in older Korean adults. Further study on causal relationships between anemia and other variables in the older population is necessary.

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Iron deficiency without anemia is responsible for decreased left ventricular function and reduced mitochondrial complex I activity in a mouse model

Cited by 38 publications

References 26 publications

Haploinsufficiency of Transferrin Receptor 1 Impairs Angiogenesis with Reduced Mitochondrial Complex I in Mice with Limb Ischemia

Haploinsufficiency of Transferrin Receptor 1 Impairs Angiogenesis with Reduced Mitochondrial Complex I in Mice with Limb Ischemia

Iron deficiency diagnosed using hepcidin on critical care discharge is an independent risk factor for death and poor quality of life at one year: an observational prospective study on 1161 patients

High anemia prevalence in Korean older adults, an advent healthcare problem: 2007–2016 KNHANES

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