Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As₂O₃)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As₂O₃ for 15 days using echocardiography, and the deposition of collagen was detected by Masson’s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As₂O₃. As₂O₃ activated the AKT/GSK-3β/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As₂O₃-treated endothelial cells. Our results highlight that As₂O₃ is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As₂O₃-induced cardiac toxicity.

The availability of simple, accurate, and affordable cuffless blood pressure (BP) devices has the potential to greatly increase the compliance with measurement recommendations and the utilization of BP measurements for BP telemonitoring. The aim of this study is to evaluate the correlation between findings from routine BP measurements using a conventional sphygmomanometer with the results from a portable ECG monitor combined with photoplethysmography (PPG) for pulse wave registration in patients with arterial hypertension. Methods: The study included 500 patients aged 32–88 years (mean 64 ± 7.9 years). Mean values from three routine BP measurements by a sphygmomanometer with cuff were selected for comparison; within one minute after the last measurement, an electrocardiogram (ECG) was recorded for 3 min in the standard lead I using a smartphone-case based single-channel ECG monitor (CardioQVARK^®-limited responsibility company “L-CARD”, Moscow, Russia) simultaneously with a PPG pulse wave recording. Using a combination of the heart signal with the PPG, levels of systolic and diastolic BP were determined based on machine learning using a previously developed and validated algorithm and were compared with sphygmomanometer results. Results: According to the Bland–Altman analysis, SD for systolic BP was 3.63, and bias was 0.32 for systolic BP. SD was 2.95 and bias was 0.61 for diastolic BP. The correlation between the results from the sphygmomanometer and the cuffless method was 0.89 (p = 0.001) for systolic and 0.87 (p = 0.002) for diastolic BP. Conclusion: Blood pressure measurements on a smartphone-case without a cuff are encouraging. However, further research is needed to improve the accuracy and reliability of clinical use in the majority of patients.

The aim of this study was to evaluate efficacy and applicability of the “intermittent hypoxic-hyperoxic exposures at rest” (IHHE) protocol as an adjuvant method for metabolic syndrome (MS) cardiometabolic components. A prospective, single-center, randomized controlled clinical study was conducted on 65 patients with MS subject to optimal pharmacotherapy, who were randomly allocated to IHHE or control (CON) groups. The IHHE group completed a 3-week, 5 days/week program of IHHE, each treatment session lasting for 45 min. The CON group followed the same protocol, but was breathing room air through a facial mask instead. The data were collected 2 days before, and at day 2 after the 3-week intervention. As the primary endpoints, systolic (SBP) and diastolic (DBP) blood pressure at rest, as well as arterial stiffness and hepatic tissue elasticity parameters, were selected. After the trial, the IHHE group had a significant decrease in SBP and DBP (Cohen’s d = 1.15 and 0.7, p < 0.001), which became significantly lower (p < 0.001) than in CON. We have failed to detect any pre-post IHHE changes in the arterial stiffness parameters (judging by the Cohen’s d), but after the intervention, cardio-ankle vascular indexes (RCAVI and LCAVI) were significantly lowered in the IHHE group as compared with the CON. The IHHE group demonstrated a medium effect (0.68; 0.69 and 0.71 Cohen’s d) in pre-post decrease of Total Cholesterol (p = 0.04), LDL (p = 0.03), and Liver Steatosis (p = 0.025). In addition, the IHHE group patients demonstrated a statistically significant decrease in pre-post differences (deltas) of RCAVI, LCAVI, all antropometric indices, NTproBNP, Liver Fibrosis, and Steatosis indices, TC, LDL, ALT, and AST in comparison with CON (p = 0.001). The pre-post shifts in SBP, DBP, and HR were significantly correlated with the reduction degree in arterial stiffness (ΔRCAVI, ΔLCAVI), liver fibrosis and steatosis severity (ΔLFibr, ΔLS), anthropometric parameters, liver enzymes, and lipid metabolism in the IHHE group only. Our results suggested that IHHE is a safe, well-tolerated intervention which could be an effective adjuvant therapy in treatment and secondary prevention of atherosclerosis, obesity, and other components of MS that improve the arterial stiffness lipid profile and liver functional state in MS patients.

Non-coding RNAs reflect many biological processes in the human body, including athero-sclerosis. In a cardiology outpatient department cohort (N = 83), we aimed to compare the levels of circulating microRNAs in groups with vulnerable plaques (N = 22), stable plaques (N = 23) and plaque-free (N = 17) depending on coronary computed tomography angiography and to evaluate associations of microRNA levels with calculated cardiovascular risks (CVR), based on the SCORE2 (+OP), ACC/AHA, ATP-III and MESA scales. Coronary computed tomography was performed on a 640-slice computed tomography scanner. Relative plasma levels of microRNA were assessed via a real-time polymerase chain reaction. We found significant differences in miR-143-3p levels (p = 0.0046 in plaque-free vs. vulnerable plaque groups) and miR-181b-5p (p = 0.0179 in stable vs. vulnerable plaques groups). Analysis of microRNA associations with CVR did not show significant differences for SCORE2 (+OP) and ATPIII scales. MiR-126-5p and miR-150-5p levels were significantly higher (p < 0.05) in patients with ACC/AHA risk >10% and miR-145-5p had linear relationships with ACC/AHA score (adjusted p = 0.0164). The relative plasma level of miR-195 was higher (p < 0.05) in patients with MESA risk > 7.5% and higher (p < 0.05) in patients with zero coronary calcium index (p = 0.036). A linear relationship with coronary calcium was observed for miR-126-3p (adjusted p = 0.0484). A positive correlation with high coronary calcium levels (> 100 Agatson units) was found for miR-181-5p (p = 0.036). Analyzing the biological pathways of these microRNAs, we suggest that miR-143-3p and miR-181-5p can be potential markers of the atherosclerosis process. Other miRNAs (miR-126-3p, 126-5p, 145-5p, 150-5p, 195-5p) can be considered as potential cardiovascular risk modifiers, but it is necessary to validate our results in a large prospective trial.

Atherosclerotic diseases of coronary vessels are the main reasons of myocardial ischemia. The value of the fractional flow reserve (FFR) factor is the golden standard for making decision on coronary network surgical treatment. The FFR measurements require expensive endovascular diagnostics. We propose a noninvasive method of the virtual FFR assessment in patient-specific coronary network based on angiography and computer tomography data. Also we analyze sensitivity of the model to the heart stroke volume.

In this work we present a one-dimensional (1D) mathematical model of the coronary circulation and use it to study the effects of arrhythmias on coronary blood flow (CBF). Hydrodynamical models are rarely used to study arrhythmias’ effects on CBF. Our model accounts for action potential duration, which updates the length of systole depending on the heart rate. It also includes dependency of stroke volume on heart rate, which is based on clinical data. We apply the new methodology to the computational evaluation of CBF during interventricular asynchrony due to cardiac pacing and some types of arrhythmias including tachycardia, bradycardia, long QT syndrome and premature ventricular contraction (bigeminy, trigeminy, quadrigeminy). We find that CBF can be significantly affected by arrhythmias. CBF at rest (60 bpm) is 26% lower in LCA and 22% lower in RCA for long QT syndrome. During bigeminy, trigeminy and quadrigeminy, respectively, CBF decreases by 28%, 19% and 14% with respect to a healthy case.