Heart failure (HF) has become an emerging problem, especially in regions where life expectancy is increasing. Despite its prevalence, the mechanisms behind HF development are not well understood, which is reflected in the lack of curative therapies. Mitochondria, autophagy, and sirtuins form a crucial triad involved in HF pathogenesis, interconnected by oxidative stress. Identifying a common pathway involving these three components could be valuable in developing new treatment strategies. Since HF is the end result of several cardiovascular diseases, this review highlights the main HF precursors and explores the roles of mitochondrial quality control (mtQC), autophagy, and sirtuins in HF development. Dysfunctional mitochondria may play a key role by enhancing oxidative stress and influencing autophagy and sirtuins, both of which possess antioxidant properties. The dual nature of autophagy—its pro-life and pro-death roles—may contribute to different outcomes in HF related to oxidative stress. As mtQC, autophagy, and sirtuins may interact, we present data on their mutual dependencies in HF. However, the specificity of these interactions remains unclear and needs further investigation, which could help identify new therapeutic targets. In conclusion, the interplay between mtQC, autophagy, and sirtuins may be crucial in HF pathogenesis and could be leveraged in developing HF treatments.

Epigenetic studies in migraine provided results on the occurrence or lack of epigenetic modifications of genes whose products are important in migraine pathogenesis. However, these studies focus on single genes without analyzing how epigenetic modifications can affect complex signaling pathways. This narrative/hypothesis review aims to provide information on how the reactive oxygen and nitrogen species (RONS)-transient receptor potential cation channel subfamily A member 1 (TRPA1)-calcitonin gene-related peptide (CGRP) axis functions, suggesting that its epigenetic modifications could be a significant factor in migraine pathophysiology. Oxidative stress is both a cause and a consequence of migraine, and reactive oxygen and nitrogen species (RONS), like other noxious stimuli, may activate the transient receptor potential cation channel subfamily A member 1 (TRPA1) to send pain signals. Methylation of the TRPA1 gene correlates with various pain states; however, the results of these studies are largely inconsistent. DNA methylation and the action of non-coding RNAs are important in the alternative RNA processing of the calcitonin-related polypeptide alpha (CALCA) gene and its transcript to produce calcitonin gene-related peptide (CGRP). The release of CGRP and substance P from trigeminal neuron terminals, mediated by TRPA1 activation and involving mitogen-activated protein kinase 1/2, is a primary mechanism driving migraine headaches. Epigenetic memory may be related to neural plasticity and migraine chronification. Therefore, the RONS-TRPA1-CGRP signaling pathways may be important in migraine pathogenesis, as demonstrated in experimental animals by the phenomenon of cortical spreading depolarization. The RONS-TRPA1-CGRP axis plays a significant role in the pathogenesis of migraine and other pain-related syndromes. Epigenetic modifications of the genes encoding the components of the antioxidant defense system, TRPA1 and CGRP, are crucial in migraine pathogenesis, prevention, and therapy. However, due to the sequence specificity of the axis, only non-coding RNAs can currently be considered for therapeutic intervention in migraine, targeting the epigenetic profile of the RONS-TRPA1-CGRP axis.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Yet, its treatment has serious challenges and is unsuccessful in a considerable fraction of patients. One reason may be a limited understanding of the molecular mechanisms underlying AF. Recent studies suggest that oxidative stress is involved in AF pathogenesis. Enhanced oxidative stress is largely determined by disrupted mitochondrial homeostasis, as cardiomyocytes heavily rely on mitochondrial energy production and calcium transfer between mitochondria and the sarcoplasmic reticulum. Atrial fibrillation involves metabolic, structural, and electrical remodeling, all of which are influenced by mitochondrial mechanisms. Mitochondrial homeostasis is controlled by mitochondrial quality control (mtQC), which is a multi-pathway mechanism to maintain integrity and functionality of mitochondria. Impaired mtQC may result in disturbed mitochondria-related calcium handling, decreased energy production, mitochondria-related inflammation and fibrosis, and impaired mitophagy. Sirtuins (SIRTs) are a family of seven members of histone deacetylases which have antioxidant properties, and three of them are localized to mitochondria. Therefore, at least some SIRTs may ameliorate enhanced oxidative stress related to damaged mitochondria. SIRTs have shown potential to improve AF outcomes in studies on AF patients and animal models. Therefore, SIRTs may have potential to ameliorate AF by decreasing oxidative stress and restoring mitochondrial homeostasis disrupted in AF. In this narrative review, we provide information on how mitochondrial dysfunctions, expressed as a disturbance in mtQC, contribute to AF through oxidative stress, calcium handling abnormalities, energy deficiency, inflammation and fibrosis, and genetic changes. In addition, we present the protective potential of sirtuins in AF.

Heart failure (HF) has become an emerging problem, especially in regions where life expectancy is increasing. Despite its prevalence, the mechanisms behind HF development are not well understood, which is reflected in the lack of curative therapies. Mitochondria, autophagy, and sirtuins form a crucial triad involved in HF pathogenesis, interconnected by oxidative stress. Identifying a common pathway involving these three components could be valuable in developing new treatment strategies. Since HF is the end result of several cardiovascular diseases, this review highlights the main HF precursors and explores the roles of mitochondrial quality control (mtQC), autophagy, and sirtuins in HF development. Dysfunctional mitochondria may play a key role by enhancing oxidative stress and influencing autophagy and sirtuins, both of which have antioxidant properties. The dual nature of autophagy—its pro-life and pro-death roles—may contribute to different outcomes in HF related to oxidative stress. As mtQC, autophagy, and sirtuins may interact, we present data on their mutual dependencies in HF. However, the specificity of these interactions remains unclear and warrants further research, which could lead to identifying new therapeutic targets. In conclusion, the interplay between mtQC, autophagy, and sirtuins may be important in HF pathogenesis and could be leveraged in developing HF treatments.

Acute coronary syndromes (ACS) are a leading cause of death and impairment in the adult population. Precise identification and modification of risk factors is crucial for a favorable clinical outcome. In this review, we aim to provide a comprehensive overview of the significance of iron deficiency (ID) in patients with ACS, particularly myocardial infarction (MI). The paper evaluates the impact of ID on the prognosis of ACS patients, highlighting its potential influence on myocardial healing, regeneration and cardiovascular events during the follow-up period. The findings suggest that iron deficiency may have a negative impact on the prognosis of patients with MI, resulting in worse quality of life, physical capacity and higher rehospitalization rates in comparison to patients with normal iron status. Iron supplementation in patients with MI could be beneficial and may have an effect on myocardial healing and left ventricular remodeling.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Yet, its treatment has serious challenges and is unsuccessful in a considerable fraction of pa-tients. One reason may be a limited understanding of the molecular mechanisms un-derlying AF. Recent studies suggest that oxidative stress is involved in AF pathogenesis. Enhanced oxidative stress is largely determined by disrupted mitochondrial homeo-stasis, as cardiomyocytes heavily rely on mitochondrial energy production and calcium transfer between mitochondria and the sarcoplasmic reticulum. Atrial fibrillation in-volves metabolic, structural, and electrical remodeling, all of which are influenced by mitochondrial mechanisms. Mitochondrial homeostasis is controlled by mitochondrial quality control (mtQC), which is a multi-pathway mechanism to maintain integrity and functionality of mitochondria. Impaired mtQC may result in disturbed mitochon-dria-related calcium handling, decreased energy production, mitochondria-related in-flammation and fibrosis, and impaired mitophagy. Sirtuins (SIRTs) are family of 7 members of histone deacetylases, which have antioxidant properties and 3 of them are localized to mitochondria. Therefore, at least some of SIRTs may ameliorate enhanced oxidative stress related to damaged mitochondria. SIRTs have shown potential to im-prove AF outcomes in studies on AF patients and animal models. Therefore, SIRTs may have a potential to ameliorate AF through decreasing oxidative stress and restoring mitochondrial homeostasis disrupted in AF. In this narrative review we provide in-formation how mitochondrial dysfunctions, expressed as the disturbance in mtQC, contributes to AF through oxidative stress, calcium handling abnormalities, energy de-ficiency, inflammation and fibrosis, and genetic changes. In addition, we presented the protective potential of sirtuins in AF.