The Regulation Mechanisms and Clinical Application of MicroRNAs in Myocardial Infarction: A Review of the Recent 5 Years

Myocardial infarction (MI) is the most frequent end-point of cardiovascular pathology, leading to higher mortality worldwide. Due to the particularity of the heart tissue, patients who experience ischemic infarction of the heart, still suffered irreversible damage to the heart even if the vascular reflow by treatment, and severe ones can lead to heart failure or even death. In recent years, several studies have shown that microRNAs (miRNAs), playing a regulatory role in damaged hearts, bring light for patients to alleviate MI. In this review, we summarized the effect of miRNAs on MI with some mechanisms, such as apoptosis, autophagy, proliferation, inflammatory; the regulation of miRNAs on cardiac structural changes after MI, including angiogenesis, myocardial remodeling, fibrosis; the application of miRNAs in stem cell therapy and clinical diagnosis; other non-coding RNAs related to miRNAs in MI during the past 5 years.

Circulating Blood-Based Biomarkers in Pulmonary Hypertension

Pulmonary hypertension (PH) is a serious hemodynamic condition, characterized by increased pulmonary vascular resistance (PVR), leading to right heart failure (HF) and death when not properly treated. The prognosis of PH depends on etiology, hemodynamic and biochemical parameters, as well as on response to specific treatment. Biomarkers appear to be useful noninvasive tools, providing information about the disease severity, treatment response, and prognosis. However, given the complexity of PH, it is impossible for a single biomarker to be adequate for the broad assessment of patients with different types of PH. The search for novel emerging biomarkers is still ongoing, resulting in a few potential biomarkers mirroring numerous pathophysiological courses. In this review, markers related to HF, myocardial remodeling, inflammation, hypoxia and tissue damage, and endothelial and pulmonary smooth muscle cell dysfunction are discussed in terms of diagnosis and prognosis. Extracellular vesicles and other markers with complex backgrounds are also reviewed. In conclusion, although many promising biomarkers have been identified and studied in recent years, there are still insufficient data on the application of multimarker strategies for monitoring and risk stratification in PH patients.

Mitochondrial Metabolism in Myocardial Remodeling and Mechanical Unloading: Implications for Ischemic Heart Disease

Ischemic heart disease refers to myocardial degeneration, necrosis, and fibrosis caused by coronary artery disease. It can lead to severe left ventricular dysfunction (LVEF ≤ 35–40%) and is a major cause of heart failure (HF). In each contraction, myocardium is subjected to a variety of mechanical forces, such as stretch, afterload, and shear stress, and these mechanical stresses are clinically associated with myocardial remodeling and, eventually, cardiac outcomes. Mitochondria produce 90% of ATP in the heart and participate in metabolic pathways that regulate the balance of glucose and fatty acid oxidative phosphorylation. However, altered energetics and metabolic reprogramming are proved to aggravate HF development and progression by disturbing substrate utilization. This review briefly summarizes the current insights into the adaptations of cardiomyocytes to mechanical stimuli and underlying mechanisms in ischemic heart disease, with focusing on mitochondrial metabolism. We also discuss how mechanical circulatory support (MCS) alters myocardial energy metabolism and affects the detrimental metabolic adaptations of the dysfunctional myocardium.

Cardiac Remodeling and Repair: Recent Approaches, Advancements, and Future Perspective

The limited ability of mammalian adult cardiomyocytes to proliferate following an injury to the heart, such as myocardial infarction, is a major factor that results in adverse fibrotic and myocardial remodeling that ultimately leads to heart failure. The continued high degree of heart failure-associated morbidity and lethality requires the special attention of researchers worldwide to develop efficient therapeutics for cardiac repair. Recently, various strategies and approaches have been developed and tested to extrinsically induce regeneration and restoration of the myocardium after cardiac injury have yielded encouraging results. Nevertheless, these interventions still lack adequate success to be used for clinical interventions. This review highlights and discusses both cell-based and cell-free therapeutic approaches as well as current advancements, major limitations, and future perspectives towards developing an efficient therapeutic method for cardiac repair.

Relationships between values of myocardial remodeling parameters and level of apoptosis biomarkers in patients with ischemic cardiomyopathy

The aim of the research. To study levels of the apoptosis biomarkers annexin A5 (AnxA5) and Bcl‑2 and to identify the presence of correlations of structural and functional parameters of the myocardium with the level of the studied biomarkers in patients with ischemic cardiomyopathy (ICMP).Materials and methods. Patients with ICMP (n = 47) were examined as the main group. The control group included 30 somatically healthy individuals. Bcl‑2 and APA5 levels were determined in the blood serum by the enzyme immunoassay.Results. It was found that in the group of patients with ICMP. The level of AnxA5 was statistically significantly higher (p < 0.001), and the level of Bcl‑2 was statistically significantly lower (p < 0.001) than in the control group. Based on the results of the correlation analysis a noticeable close relationship on the Cheddock scale was revealed between levels of the studied apoptosis biomarkers and the values of the sphericity index of in diastole and systole of left ventricle (LV), final diastolic and systolic volume of LV and ejection fraction of LV. Between the other parameters of myocardial remodeling and levels of the studied biomarkers of apoptosis, the closeness of relationships on the Cheddock scale were weak and moderate.

Receptor Interacting Protein Kinases 1/3: The Potential Therapeutic Target for Cardiovascular Inflammatory Diseases

The receptor interacting protein kinases 1/3 (RIPK1/3) have emerged as the key mediators in cell death pathways and inflammatory signaling, whose ubiquitination, phosphorylation, and inhibition could regulate the necroptosis and apoptosis effectually. Recently, more and more studies show great interest in the mechanisms and the regulator of RIPK1/3-mediated inflammatory response and in the physiopathogenesis of cardiovascular diseases. The crosstalk of autophagy and necroptosis in cardiomyocyte death is a nonnegligible conversation of cell death. We elaborated on RIPK1/3-mediated necroptosis, pathways involved, the latest regulatory molecules and therapeutic targets in terms of ischemia reperfusion, myocardial remodeling, myocarditis, atherosclerosis, abdominal aortic aneurysm, and cardiovascular transplantation, etc.

Relationship between electrical myocardial instability and postinfarction remodeling in patients with ST-segment elevation myocardial infarction

Aim To study the clinical value of markers for myocardial electrical instability in combination with echocardiographic parameters for predicting the risk of cardiovascular complications (CVC) in the postinfarction period.Material and methods This study included 118 patients with ST segment elevation myocardial infarction (STEMI) and hemodynamically significant stenosis of one coronary artery. A percutaneous coronary intervention (PCI) with stenting of the infarct-related artery was performed for all patients. On day 7-9 and at 24 and 48 weeks after the treatment, ECG Holter monitoring was performed, which included analyses of ventricular late potentials, dispersion of QT interval duration, heart rate turbulence (HRT) and variability (HRV), and heart chronotropic load (HCL). At baseline and during postinfarction week 12, all patients underwent echocardiography with calculation of indexes of end-diastolic volume (iEDV) and end-systolic volume (iESV) to verify the signs of left ventricular (LV) myocardial remodeling. The criteria for LV pathological remodeling included increases in iEDV >20 % and/or iESV >15 % at 12 weeks after STEMI. The group without remodeling, R(-), consisted of 79 (67 %) patients and the group with signs of LV pathological remodeling, R(+), consisted of 39 (33 %) patients. Quality of life and achieved endpoints were evaluated during 144 weeks.Results By week 48 in group R(-), the stabilization of electrical processes in the myocardium was more pronounced as indicated by a decrease in HFLA by 12 % (р=0.004) and by a fourfold increase in RMS (р=0.047). Only in this group, the baroreflex sensitivity restored; pathological ТРС decreased from 20 to 5% (p=0.002) by the end of the active treatment. Stabilization of the repolarization phase duration in various parts of the myocardium was more active in patients without pathological remodeling as shown by decreases in disp QTa (р=0.009), disp QTe (р=0.03), sd QTa (р=0.006), and sd QTe (р=0.009). This was not observed in the group R(+). The recovery of vagosympathetic balance due to leveling the sympathetic component also was more effective in the group R(-), which was reflected in increased spectral and temporal HRV indexes (р<0.05). Both groups showed reduced HCL values at 24 weeks (р=0.047 and р=0.006); however, the HCL regression remained also at 48 weeks only in the group R(-) (р=0.006). Group R(-) patients reported higher quality of life (р=0.03) than group R(+) patients. Endpoints were achieved more frequently in the group R(+): 87.1 % vs. 27.8 % (odds ratio, 11.8; 95 % confidence interval, 4.6–30.8; р=0.00001).Conclusion Pathological myocardial remodeling in early postinfarction period is associated with electrophysiological instability of the myocardium, which results in the development of CVC and low quality of life in patients with STEMI.

AGE AND GENDERS DIFFERENCES OF MORPHOFUNCTIONAL PARAMETERS OF THE HEART IN COMORBID PATIENTS

Women with a long course of hypertension, which leads to the development of chronic heart failure, valid factors are the presence of diabetes mellitus, coronary artery disease and the advantage of a favorable concentric type of LV remodeling with preserved systolic function. In men of the same age, myocardial remodeling has a less favorable course with an increase in the size of the left ventricle and LA on the background of a more pronounced decrease in systolic function.