miR-190a-5p Partially Represses the Abnormal Electrical Activity of SCN3B in Cardiac Arrhythmias by Downregulation of IL-2

Cardiac arrhythmias (CAs) are generally caused by disruption of the cardiac conduction system; interleukin-2 (IL-2) is a key player in the pathological process of CAs. This study aimed to investigate the molecular mechanism underlying the regulation of IL-2 and the sodium channel current of sodium voltage-gated channel beta subunit 3 (SCN3B) by miR-190a-5p in the progression of CAs. ELISA results suggested the concentration of peripheral blood serum IL-2 in patients with atrial fibrillation (AF) to be increased compared to that in normal controls; fluorescence in situ hybridization indicated that the expression of IL-2 in the cardiac tissues of patients with AF to be upregulated and that miR-190a-5p to be downregulated. Luciferase reporter assay, quantitative real-time-PCR, and whole-cell patch-clamp experiments confirmed the downregulation of IL-2 by miR-190a-5p and influence of the latter on the sodium current of SCN3B. Overall, miR-190a-5p suppressed the increase in SCN3B sodium current caused by endogenous IL-2, whereas miR-190a-5p inhibitor significantly reversed this effect. IL-2 was demonstrated to be directly regulated by miR-190a-5p. We, therefore, concluded that the miR-190a-5p/IL-2/SCN3B pathway could be involved in the pathogenesis of CAs and miR-190a-5p might acts as a potential protective factor in pathogenesis of CAs.

Dynamical behavior of cardiac conduction system under external disturbances: simulation based on microcontroller technology

The heart rhythm is one of the most interesting aspects of the dynamic behavior of biological systems. Understanding heart rhythms is essential in the dynamic analysis of the heart. Each type of dynamic behaviour can describe normal or pathological physiology. The heart is made up of nodes ranging from SA node (natural pacemaker) to Purkinje fibers. The electric current originates in the sinus node and travels through the heart until it reaches the Purkinje fibers, causing after its passage through each of the nodes a heartbeat thus constituting the electrocardiogram (ECG). Since the origin of the electric current is the sinus node, in this article we study numerically and experimentally by microcontroller the influence of the sinus node on the propagation of electric current through the heart. A study of the sinus node in its autonomous state shows us that in their coupled state, the nodes of the heart qualitatively reproduce the time series of the action potential of this latter, which leads to the recording of the ECG. A study when the sinus node is subjected to periodic pulsed excitation E 1(t) = kP(t), assumed to come from blood pressure, with P(t) the blood pressure, shows that for some selected frequencies, it is found that the nodes of the heart and the ECG exhibit responses having the same shape and the same frequencies as those of the pulsatile blood pressure. This suggests the possibility of using such a conversion and excitation mechanism to replicate the functioning of cardiac conduction system. The chaotic analysis of the sinus node subjected to a sinusoidal type disturbance (E 0sin(ωt)) is also presented, it shows that in its chaotic state, the nodes of the heart, as well as the ECG, provide very high frequency signals. This requires the control of the sinus node (natural pacemaker) in such a situation

Ageing, Age-Related Cardiovascular Risk and the Beneficial Role of Natural Components Intake

Ageing, in a natural way, leads to the gradual worsening of the functional capacity of all systems and, eventually, to death. This process is strongly associated with higher metabolic and oxidative stress, low-grade inflammation, accumulation of DNA mutations and increased levels of related damage. Detrimental changes that accumulate in body cells and tissues with time raise the vulnerability to environmental challenges and enhance the risk of major chronic diseases and mortality. There are several theses concerning the mechanisms of ageing: genetic, free radical telomerase, mitochondrial decline, metabolic damage, cellular senescence, neuroendocrine theory, Hay-flick limit and membrane theories, cellular death as well as the accumulation of toxic and non-toxic garbage. Moreover, ageing is associated with structural changes within the myocardium, cardiac conduction system, the endocardium as well as the vasculature. With time, the cardiac structures lose elasticity, and fibrotic changes occur in the heart valves. Ageing is also associated with a higher risk of atherosclerosis. The results of studies suggest that some natural compounds may slow down this process and protect against age-related diseases. Animal studies imply that some of them may prolong the lifespan; however, this trend is not so obvious in humans.

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts

Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset <18 years, and all available first- and second-degree relatives. Fifteen patients (88.2%) were male, and sixteen independent variants were found (twelve missense, three truncating and one complex inframe deletion/insertion). The frequency of compound heterozygosity was remarkably high (3/17, 17.6%), with early childhood onset and severe disease. Overall, 70.6% of pediatric patients presented with overlap syndrome, 11.8% with isolated sick sinus syndrome, 11.8% with isolated Brugada syndrome (BrS) and 5.9% with isolated type 3 long QT syndrome (LQTS). A total of 24/45 SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.

Abnormal Expression of Connexin43 in Cardiac Injury Induced by S-Band and X-Band Microwave Exposure in Rats

Although the effects of microwave exposure on the heart have gradually become the focus of domestic and foreign scholars, the biological effects caused by different doses and different frequency bands of exposure are still unclear. In this study, we will investigate the damaging effect of S-band and X-band microwave composite exposure on cardiac structure and function, as well as the pathophysiological significance of Cx43 in cardiac conduction dysfunction after exposure. We used S- and X-band radiation sources with the average power density of 5 and 10 mW/cm2 to expose Wistar rats to single or composite exposure. At the 6th hour, on the 7th, 14th, and 28th days after exposure, ECG was used to detect the electrical conduction of the heart, and the myocardial enzyme was measured by the automatic biochemical analyzer. We selected the observation time points and groups with severe damage to observe the changes of myocardial structure and ultrastructure with an optical microscope and TEM; and to detect the expression and distribution of Cx43 by western blotting and immunohistochemistry. After exposure, the heart rate increased, the P wave amplitude decreased, and the R wave amplitude increased; the content of the myocardial enzyme in serum increased; the structure and ultrastructure of cardiac tissue were damaged. The damage was dose-dependent and frequency-dependent. The expression of Cx43 in myocardial tissue decreased, and distribution was abnormal. Taken together, these findings suggested that the mechanism of abnormal electrical conduction in the heart of rats by S- and X-band microwave exposure might be related to the decreased expression and disordered distribution of Cx43 after microwave exposure.

Skin score as a predictor of prolonged QTc in systemic sclerosis.

Background Systemic sclerosis is an autoimmune disease characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Cardiac involvement during systemic sclerosis can be primary or secondary to pulmonary arterial hypertension and renal pathology. Among the disorders in systemic sclerosis, prolongation of QTc time is also associated with more anti-RNA polymerase III antibodies, longer duration and severity of disease. Methods This case-control study was performed on 35 patients with systemic scleroderma who filled in the American Society of Rheumatism (ACR / EULAR criteria) and 35 healthy subjects prior to entering the study. Then, the QTc distance was extracted from the electrocardiogram and calculated using the formula. The measured QTc distance in the electrocardiogram, QTc> 440ms in men and QTc> 460ms in women, was defined as QTc long. Then the patients and the control group underwent echocardiography and changes in QTc interval and its relation with echocardiographic findings was evaluated. Results The results of this study indicated a significant relationship between QTc distance in patients with scleroderma compared with healthy controls. There was also a significant relationship between QTc and Skin Score of patients. However, there was no significant correlation between QTc distance and age, gender, duration of disease, Anti-Centromere, Anti-Scl70, and pulmonary artery pressure. Conclusion This study concludes that patients with scleroderma are at high risk for cardiac conduction impairment. The only factor that significantly correlated with QTc was the Skin Score of the patients.

Next-generation pacemakers: from electrical devices to biological pacemakers

The invention of an electric pacemaker in the middle of the 20th century led to a revolution in the treatment of cardiac conduction system diseases. The improvement of pacemakers continued. In 1962, the first small series of external pacemakers for percutaneous and direct stimulation was produced in Kaunas. After a while, electric pacemakers became more reliable, smaller and lighter in weight, but the problem of foreign body associated infection and limited service life remained unresolved. Modern high-tech medicine strives to create less invasive electric pacemakers, but nevertheless, biological pacemakers can expand the therapeutic arsenal for the treatment of cardiac patients, being the most physiological for humans. The concept of an artificial biological pacemaker consists of the creation of an organic structure that generates a spontaneous rhythm from the implantation site in the myocardium. Various gene and cellular approaches were used to create biological pacemakers: a functional reorganization approach (use of adenovirus vectors for hyperexpression of genes encoding ion channels in cardiomyocytes); hybrid approach (use of fibroblasts to deliver genes of ion channels that provide heart automation); somatic reprogramming approach (overexpression of the transcription factor TBX18 using adenoviral vectors, which reprograms cardiomyocytes into induced sinoatrial node cells, creating cardiac stimulatory activity); cellular approach (transplantation of stem cells to a specific place in the heart, thereby creating biological stimulation). Modern methods of electrical cardiac stimulation and the developed concepts of the biological pacemaker clearly show the possibility of eliminating current problems associated with the use of an artificial pacemaker by replacing it with a biological one. Each of the approaches (gene, cellular, hybrid-cellular, somatic reprogramming) has its own advantages and disadvantages, which predisposes to further study and improvement in order to introduce a biological pacemaker into clinical practice.

miR-208a in Cardiac Hypertrophy and Remodeling

Various stresses, including pressure overload and myocardial stretch, can trigger cardiac remodeling and result in heart diseases. The disorders are associated with high risk of morbidity and mortality and are among the major health problems in the world. MicroRNAs, a class of ~22nt-long small non-coding RNAs, have been found to participate in regulating heart development and function. One of them, miR-208a, a cardiac-specific microRNA, plays key role(s) in modulating gene expression in the heart, and is involved in a broad array of processes in cardiac pathogenesis. Genetic deletion or pharmacological inhibition of miR-208a in rodents attenuated stress-induced cardiac hypertrophy and remodeling. Transgenic expression of miR-208a in the heart was sufficient to cause hypertrophic growth of cardiomyocytes. miR-208a is also a key regulator of cardiac conduction system, either deletion or transgenic expression of miR-208a disturbed heart electrophysiology and could induce arrhythmias. In addition, miR-208a appeared to assist in regulating the expression of fast- and slow-twitch myofiber genes in the heart. Notably, this heart-specific miRNA could also modulate the “endocrine” function of cardiac muscle and govern the systemic energy homeostasis in the whole body. Despite of the critical roles, the underlying regulatory networks involving miR-208a are still elusive. Here, we summarize the progress made in understanding the function and mechanisms of this important miRNA in the heart, and propose several topics to be resolved as well as the hypothetical answers. We speculate that miR-208a may play diverse and even opposite roles by being involved in distinct molecular networks depending on the contexts. A deeper understanding of the precise mechanisms of its action under the conditions of cardiac homeostasis and diseases is needed. The clinical implications of miR-208a are also discussed.