Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many signaling pathways. However, if overproduced, they also play a significant role in the development of cardiovascular diseases, such as arrhythmia, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction and heart transplantation), and heart failure. As a result of oxidative stress action, apoptosis, hypertrophy, and fibrosis may occur. MicroRNAs (miRNAs) represent important endogenous nucleotides that regulate many biological processes, including those involved in heart damage caused by oxidative stress. Oxidative stress can alter the expression level of many miRNAs. These changes in miRNA expression occur mainly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, calcineurin/nuclear factor of activated T cell (NFAT), or nuclear factor kappa B (NF-κB) pathways. Up until now, several circulating miRNAs have been reported to be potential biomarkers of ROS-related cardiac diseases, including myocardial infarction, hypertrophy, ischemia/reperfusion, and heart failure, such as miRNA-499, miRNA-199, miRNA-21, miRNA-144, miRNA-208a, miRNA-34a, etc. On the other hand, a lot of studies are aimed at using miRNAs for therapeutic purposes. This review points to the need for studying the role of redox-sensitive miRNAs, to identify more effective biomarkers and develop better therapeutic targets for oxidative-stress-related heart diseases.

Cardiovascular diseases are the most common causes of morbidity and mortality worldwide. Redox dysregulation and a dyshomeostasis of inflammation arise from, and result in, cellular aberrations and pathological conditions, which lead to cardiovascular diseases. Despite years of intensive research, there is still no safe and effective method for their prevention and treatment. Recently, molecular hydrogen has been investigated in preclinical and clinical studies on various diseases associated with oxidative and inflammatory stress such as radiation-induced heart disease, ischemia-reperfusion injury, myocardial and brain infarction, storage of the heart, heart transplantation, etc. Hydrogen is primarily administered via inhalation, drinking hydrogen-rich water, or injection of hydrogen-rich saline. It favorably modulates signal transduction and gene expression resulting in suppression of proinflammatory cytokines, excess ROS production, and in the activation of the Nrf2 antioxidant transcription factor. Although H₂ appears to be an important biological molecule with anti-oxidant, anti-inflammatory, and anti-apoptotic effects, the exact mechanisms of action remain elusive. There is no reported clinical toxicity; however, some data suggests that H₂ has a mild hormetic-like effect, which likely mediate some of its benefits. The mechanistic data, coupled with the pre-clinical and clinical studies, suggest that H₂ may be useful for ROS/inflammation-induced cardiotoxicity and other conditions.

The interest in non-coding RNAs, which started more than a decade ago, has still not weakened. A wealth of experimental and clinical studies has suggested the potential of non-coding RNAs, especially the short-sized microRNAs (miRs), to be used as the new generation of therapeutic targets and biomarkers of cardiovascular disease, an ever-growing public health issue in the modern world. Among the hundreds of miRs characterized so far, microRNA-1 (miR-1) and microRNA-21 (miR-21) have received some attention and have been associated with cardiac injury and cardioprotection. In this review article, we summarize the current knowledge of the function of these two miRs in the heart, their association with cardiac injury, and their potential cardioprotective roles and biomarker value. While this field has already been extensively studied, much remains to be done before research findings can be translated into clinical application for patient’s benefit.

There are many situations of excessive production of reactive oxygen species (ROS) such as radiation, ischemia/reperfusion (I/R), and inflammation. ROS contribute to and arises from numerous cellular pathologies, diseases, and aging. ROS can cause direct deleterious effects by damaging proteins, lipids, and nucleic acids as well as exert detrimental effects on several cell signaling pathways. However, ROS are important in many cellular functions. The injurious effect of excessive ROS can hypothetically be mitigated by exogenous antioxidants, but clinically this intervention is often not favorable. In contrast, molecular hydrogen provides a variety of advantages for mitigating oxidative stress due to its unique physical and chemical properties. H₂may be superior to conventional antioxidants, since it can selectively reduce ●OH radicals while preserving important ROS that are otherwise used for normal cellular signaling. Additionally, H₂exerts many biological effects, including antioxidation, anti-inflammation, anti-apoptosis, and anti-shock. H₂accomplishes these effects by indirectly regulating signal transduction and gene expression, each of which involves multiple signaling pathways and crosstalk. The Keap1-Nrf2-ARE signaling pathway, which can be activated by H₂, plays a critical role in regulating cellular redox balance, metabolism, and inducing adaptive responses against cellular stress. H₂also influences the crosstalk among the regulatory mechanisms of autophagy and apoptosis, which involve MAPKs, p53, Nrf2, NF-κB, p38 MAPK, mTOR, etc. The pleiotropic effects of molecular hydrogen on various proteins, molecules and signaling pathways can at least partly explain its almost universal pluripotent therapeutic potential.

Food quality and nutritional habits strongly influence human health status. Extensive research has been conducted to confirm that foods rich in biologically active nutrients have a positive impact on the onset and development of different pathological processes, including cardiovascular diseases. However, the underlying mechanisms by which dietary compounds regulate cardiovascular function have not yet been fully clarified. A growing number of studies confirm that bioactive food components modulate various signaling pathways which are involved in heart physiology and pathology. Recent evidence indicates that microRNAs (miRNAs), small single-stranded RNA chains with a powerful ability to influence protein expression in the whole organism, have a significant role in the regulation of cardiovascular-related pathways. This review summarizes recent studies dealing with the impact of some biologically active nutrients like polyunsaturated fatty acids (PUFAs), vitamins E and D, dietary fiber, or selenium on the expression of many miRNAs, which are connected with cardiovascular diseases. Current research indicates that the expression levels of many cardiovascular-related miRNAs like miRNA-21, -30 family, -34, -155, or -199 can be altered by foods and dietary supplements in various animal and human disease models. Understanding the dietary modulation of miRNAs represents, therefore, an important field for further research. The acquired knowledge may be used in personalized nutritional prevention of cardiovascular disease or the treatment of cardiovascular disorders.

The increased production of reactive oxygen species and oxidative stress are important factors contributing to the development of diseases of the cardiovascular and central nervous systems. Molecular hydrogen is recognized as an emerging therapeutic, and its positive effects in the treatment of pathologies have been documented in both experimental and clinical studies. The therapeutic potential of hydrogen is attributed to several major molecular mechanisms. This review focuses on the effects of hydrogen on the cardiovascular and central nervous systems, and summarizes current knowledge about its actions, including the regulation of redox and intracellular signaling, alterations in gene expressions, and modulation of cellular responses (e.g., autophagy, apoptosis, and tissue remodeling). We summarize the functions of hydrogen as a regulator of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated redox signaling and the association of hydrogen with mitochondria as an important target of its therapeutic action. The antioxidant functions of hydrogen are closely associated with protein kinase signaling pathways, and we discuss possible roles of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and Wnt/β-catenin pathways, which are mediated through glycogen synthase kinase 3β and its involvement in the regulation of cellular apoptosis. Additionally, current knowledge about the role of molecular hydrogen in the modulation of autophagy and matrix metalloproteinases-mediated tissue remodeling, which are other responses to cellular stress, is summarized in this review.