Pathological Roles of Iron in Cardiovascular Disease

Kobayashi, Michie; Suhara, Tomohiro; Baba, Yuichi; Kawasaki, Nicholas K.; Higa, Jason K.; Mizutani, Takashi

doi:10.2174/1389450119666180605112235

Cited by 124 publications

(99 citation statements)

References 101 publications

(122 reference statements)

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“…Heme-iron homeostasis is paradoxical in cardiac diseases, depending on the environmental conditions: local myocardial iron retention and tissue toxicity in MI [98] and systemic anemia in heart failure (HF) [99]. The frequency of anemia is around 30% in HF patients and hemoglobin is inversely correlated to left ventricle ejection fraction.…”

Section: Myocardial Infarction (Mi)mentioning

confidence: 99%

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases

Michel

Martı́n-Ventura

2020

IJMS

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As the main particulate component of the circulating blood, RBCs play major roles in physiological hemodynamics and impact all arterial wall pathologies. RBCs are the main determinant of blood viscosity, defining the frictional forces exerted by the blood on the arterial wall. This function is used in phylogeny and ontogeny of the cardiovascular (CV) system, allowing the acquisition of vasomotricity adapted to local metabolic demands, and systemic arterial pressure after birth. In pathology, RBCs collide with the arterial wall, inducing both local retention of their membranous lipids and local hemolysis, releasing heme-Fe++ with a high toxicity for arterial cells: endothelial and smooth muscle cells (SMCs) cardiomyocytes, neurons, etc. Specifically, overloading of cells by Fe++ promotes cell death. This local hemolysis is an event associated with early and advanced stages of human atherosclerosis. Similarly, the permanent renewal of mural RBC clotting is the major support of oxidation in abdominal aortic aneurysm. In parallel, calcifications promote intramural hemorrhages, and hemorrhages promote an osteoblastic phenotypic shift of arterial wall cells. Different plasma or tissue systems are able, at least in part, to limit this injury by acting at the different levels of this system.

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Section: Myocardial Infarction (Mi)mentioning

confidence: 99%

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases

Michel

Martı́n-Ventura

2020

IJMS

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“…Additionally, large amounts of iron have been suggested to possibly raise the potential risk of coronary artery diseases (Kobayashi et al, 2018). Recently, a study further illustrated that ferroptosis, which is an emerging concept of iron-dependent cell death, could regulate the fate of chemotherapy, as well as MI/R caused cardiomyopathy (Fang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

USP22 Protects Against Myocardial Ischemia–Reperfusion Injury via the SIRT1-p53/SLC7A11–Dependent Inhibition of Ferroptosis–Induced Cardiomyocyte Death

Sun

et al. 2020

Front. Physiol.

143

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Myocardial ischemia-reperfusion (MI/R) injury is characterized by iron deposition and reactive oxygen species production, which can induce ferroptosis. Ferroptosis has also been proposed to promote cardiomyocyte death. The current study sought to define the mechanism governing cardiomyocyte death in MI/R injury. An animal model of MI/R was established by ligation and perfusion of the left anterior descending coronary artery, and a cellular model of IR was constructed in cardiomyocytes. ChIP assay was then conducted to determine the interaction among USP22, SIRT1, p53, and SLC7A11. Loss-and gain-of-function assays were also conducted to determine the in vivo and in vitro roles of USP22, SIRT1, and SLC7A11. The infarct size and pathological changes of myocardial tissue were observed using TCC and hematoxylin-eosin staining, and the levels of cardiac function-and myocardial injury-related factors of rats were determined. Cardiomyocyte viability and apoptosis were evaluated in vitro, followed by detection of ferroptosis-related indicators (glutathione (GSH), reactive oxygen species, lipid peroxidation, and iron accumulation). USP22, SIRT1, and SLC7A11 expressions were found to be down-regulated, whereas p53 was highly expressed during MI/R injury. USP22, SIRT1, or SLC7A11 overexpression reduced the infarct size and ameliorated pathological conditions, cardiac function, as evidenced by reduced maximum pressure, ejection fraction, maximum pressure rate, and myocardial injury characterized by lower creatine phosphokinase and lactate dehydrogenase levels in vivo. Moreover, USP22, SIRT1, or SLC7A11 elevation contributed to enhanced cardiomyocyte viability and attenuated ferroptosis-induced cell death in vitro, accompanied by increased GSH levels, as well as decreased reactive oxygen species production, lipid peroxidation, and iron accumulation. Together, these results demonstrate that USP22 overexpression could inhibit ferroptosis-induced cardiomyocyte death to protect against MI/R injury via the SIRT1/p53/SLC7A11 association.

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“…These mechanisms keep the cytoplasmic labile iron pool (LIP) strictly controlled [85]. An imbalance of these homeostatic factors can lead to an accumulation of intracellular iron, increased reactive oxygen species, and eventually cell death [86].…”

Section: Iron Balance/homeostasismentioning

confidence: 99%

Geoengineering, Coal Fly Ash and the New Heart-Iron Connection: Universal Exposure to Iron Oxide Nanoparticulates

Whiteside¹,

Herndon²

2019

JAMMR

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Globally, air pollution is the leading environmental cause of human disease and death, and it is a major contributor to cardiovascular disease. Air pollution damages the cardiovascular system by oxidative stress, inflammation, endothelial dysfunction, and pro-thrombotic changes. Ultrafine particulate matter from the combustion of fossil fuels delivers the most potent and harmful elements of air pollution. Coal fly ash is a rich source of nano-sized metal, iron oxide, and carbonaceous particles. Previous findings revealed that coal fly ash is widely utilized in undisclosed tropospheric aerosol geoengineering. Proper iron balance is central to human health and disease, and the harmful effects of iron are normally prevented by tightly controlled processes of systemic and cellular iron homeostasis. Altered iron balance is linked to the traditional risk factors for cardiovascular disease. The iron-heart hypothesis is supported by epidemiological, clinical, and experimental studies. Biogenic magnetite (Fe3O4) serves essential life functions, but iron oxide nanoparticles from anthropogenic sources cause disease. The recent finding of countless combustion-type magnetic nanoparticles in damaged hearts of persons from highly polluted areas is definitive evidence of the connection between the iron oxide fraction of air pollution and cardiovascular disease. Spherical magnetic iron oxide particles found in coal fly ash and certain vehicle emissions match the exogenous iron pollution particles found in the human heart. Iron oxide nanoparticles cross the placenta and may act as seed material for future cardiovascular disease. The pandemic of non-communicable diseases like cardiovascular disease and also rapid global warming can be alleviated by drastically reducing nanoparticulate air pollution. It is crucial to halt tropospheric aerosol geoengineering, and to curb fine particulate emissions from industrial and traffic sources to avoid further gross contamination of the human race by iron oxide-type nanoparticles.

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Pathological Roles of Iron in Cardiovascular Disease

Cited by 124 publications

References 101 publications

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases

USP22 Protects Against Myocardial Ischemia–Reperfusion Injury via the SIRT1-p53/SLC7A11–Dependent Inhibition of Ferroptosis–Induced Cardiomyocyte Death

Geoengineering, Coal Fly Ash and the New Heart-Iron Connection: Universal Exposure to Iron Oxide Nanoparticulates

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