Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 21, Pages -Publisher
MDPI
DOI: 10.3390/ijms21217889
Keywords
iron; myocardial ischemia; reperfusion injury; reactive oxygen species; mitochondria; ferroptosis; cardioprotection
Funding
- Slovak Research and Development Agency [APVV-15-0607, APVV-15-0119, APVV-16-0263, APVV-19-0540]
- Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic (VEGA SR) [2/0160/17, 2/0141/18, 2/0121/18, 1/0055/20]
- IT Monitoring System (ITMS) [26230120009]
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Iron is an essential mineral participating in different functions of the organism under physiological conditions. Numerous biological processes, such as oxygen and lipid metabolism, protein production, cellular respiration, and DNA synthesis, require the presence of iron, and mitochondria play an important role in the processes of iron metabolism. In addition to its physiological role, iron may be also involved in the adaptive processes of myocardial conditioning. On the other hand, disorders of iron metabolism are involved in the pathological mechanisms of the most common human diseases and include a wide range of them, such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease, and accelerate the development of atherosclerosis. Furthermore, iron also exerts potentially deleterious effects that may be manifested under conditions of ischemia/reperfusion (I/R) injury, myocardial infarction, heart failure, coronary artery angioplasty, or heart transplantation, due to its involvement in reactive oxygen species (ROS) production. Moreover, iron has been recently described to participate in the mechanisms of iron-dependent cell death defined as ferroptosis. Ferroptosis is a form of regulated cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been shown to be associated with I/R injury and several other cardiac diseases as a significant form of cell death in cardiomyocytes. In this review, we will discuss the role of iron in cardiovascular diseases, especially in myocardial I/R injury, and protective mechanisms stimulated by different forms of conditioning with a special emphasis on the novel targets for cardioprotection.
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