Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension.

The oxidative stress plays an important role in the development of cardiovascular diseases (CVD). In CVD progression an aberrant redox regulation was observed. In this regulation levels of reactive oxygen species (ROS) play an important role in cellular signaling, where Nrf2 is the key regulator of redox homeostasis. Keap1-Nrf2-ARE system regulates a great set of detoxificant and antioxidant enzymes in cells after ROS and electrophiles exposure. In this review we focus on radical-generating systems in cardiovascular system as well as on Nrf2 as a target against oxidative stress and a key player of redox regulation in cardiovascular diseases. We also summarize the current knowledge about the role of Nrf2 in pathophysiology of several CVD (hypertension, cardiac hypertrophy, cardiomyopathies) as well as in cardioprotection against myocardial ischemia/ reperfusion injury.

Quercetin (QCT) is flavonoid that possesses various biological functions including anti-oxidative and radical-scavenging activities. Moreover, QCT exerts some preventive actions in treatment of cardiovascular diseases. The aim of present study was to explore effects of prolonged administration of QCT on changes induced by repeated application of doxorubicin (DOX) in rat hearts. We focused on the ultrastructure of myocardium, matrix metalloproteinases (MMPs), biometric parameters, and apoptosis induction. Our aim was also to examine effects of QCT on ischemic tolerance in hearts exposed to chronic effects of DOX, and to determine possible mechanisms underlying effects of QCT. Our results showed that QCT prevented several negative chronic effects of DOX: (I) reversed DOX-induced blood pressure increase; (II) mediated improvement of deleterious effects of DOX on ultrastructure of left ventricle; (III) prevented DOX-induced effects on tissue MMP-2 activation; and (iv) reversed effects of DOX on apoptosis induction and superoxide dismutase inhibition. Moreover, we showed that rat hearts exposed to effects of QCT were more resistant to ischemia/reperfusion injury. Effects of QCT on modulation of ischemic tolerance were linked to Akt kinase activation and connexin-43 up-regulation. Taken together, these results demonstrate that prolonged treatment with QCT prevented negative chronic effects of DOX on blood pressure, cellular damage, MMP-2 activation, and apoptosis induction. Moreover, QCT influenced myocardial responses to acute ischemic stress. These facts bring new insights into mechanisms of QCT action on rat hearts exposed to the chronic effects of DOX.

Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions.

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.