Metabolic syndrome (MetS) significantly increases the risk of cardiovascular diseases (CVD), a leading cause of death globally. The presented study investigated the cardioprotective role of dietary polyphenols found in pomegranate peels in an animal model of metabolic syndrome. Zucker diabetic fatty rats (ZDF, MetS rats, fa/fa) were supplemented with polyphenol-rich pomegranate peel extract (EPP) at two dosages: 100 mg/kg BW and 200 mg/kg BW. The extract was administered for 8 weeks. The effect of ethanolic peel extract on the concentration of oxidative stress markers (CAT, SOD, MnSOD, GR, GST, GPx, TOS, SH, and MDA), biomarkers of heart failure (cTnI, GAL-3), and alternations in tissue architecture was assessed. The results showed a significant increase in SH concentration mediated via EPP supplementation (p < 0.001). Treatment with a 100 mg/kg BW dosage reduced the TOS level more efficiently than the higher dose. Interestingly, the CAT and GST activities were relevantly higher in the MetS 100 group (p < 0.001) compared to the MetS control. The rats administered EPP at a dose of 200 mg/kg BW did not follow a similar trend. No differences in the GR (p = 0.063), SOD (p = 0.455), MnSOD (p = 0.155), and MDA (p = 0.790) concentration were observed after exposure to the pomegranate peel extract. The administration of EPP did not influence the cTnI and GAL-3 levels. Histology analysis of the heart and aorta sections revealed no toxic changes in phenolic-treated rats. The findings of this study prove that the extract from pomegranate peels possesses free radical scavenging properties in the myocardium. The effect on alleviating ventricular remodeling and cardiomyocyte necrosis was not confirmed and requires further investigation.

Despite advances in the management of iron deficiency in heart failure (HF), the mechanisms underlying the effects of treatment remain to be established. Iron distribution and metabolism in HF pathogenesis need to be clarified. We used a porcine tachycardia-induced cardiomyopathy model to find out how HF development influences hepatic and myocardial iron storing, focusing on ferritin, the main iron storage protein. We found that cumulative liver congestion (due to the decrease of heart function) overwhelms its capacity to recycle iron from erythrocytes. As a consequence, iron is trapped in the liver as poorly mobilized hemosiderin. What is more, the ferritin-bound Fe³⁺ (reflecting bioavailable iron stores), and assembled ferritin (reflecting ability to store iron) are decreased in HF progression in the liver. We demonstrate that while HF pigs show iron deficiency indices, erythropoiesis is enhanced. Renin–angiotensin–aldosterone system activation and hepatic hepcidin suppression might indicate stress erythropoiesisinduced in HF. Furthermore, assembled ferritin increases but ferritin-bound Fe³⁺ is reduced in myocardium, indicating that a failing heart increases the iron storage reserve but iron deficiency leads to a drop in myocardial iron stores. Together, HF in pigs leads to down-regulated iron bioavailability and reduced hepatic iron storage making iron unavailable for systemic/cardiac needs.

Cardiac fibroblasts and cardiomyocytes are the main cells involved in the pathophysiology of myocarditis (MCD). These cells are especially sensitive to changes in iron homeostasis, which is extremely important for the optimal maintenance of crucial cellular processes. However, the exact role of iron status in the pathophysiology of MCD remains unknown. We cultured primary human cardiomyocytes (hCM) and cardiofibroblasts (hCF) with sera from acute MCD patients and healthy controls to mimic the effects of systemic inflammation on these cells. Next, we performed an initial small-scale (n = 3 per group) RNA sequencing experiment to investigate the global cellular response to the exposure on sera. In both cell lines, transcriptomic data analysis revealed many alterations in gene expression, which are related to disturbed canonical pathways and the progression of cardiac diseases. Moreover, hCM exhibited changes in the iron homeostasis pathway. To further investigate these alterations in sera-treated cells, we performed a larger-scale (n = 10 for controls, n = 18 for MCD) follow-up study and evaluated the expression of genes involved in iron metabolism. In both cell lines, we demonstrated an increased expression of transferrin receptor 1 (TFR1) and ferritin in MCD serum-treated cells as compared to controls, suggesting increased iron demand. Furthermore, we related TFR1 expression with the clinical profile of patients and showed that greater iron demand in sera-treated cells was associated with higher inflammation score (interleukin 6 (IL-6), C-reactive protein (CRP)) and advanced neurohormonal activation (NT-proBNP) in patients. Collectively, our data suggest that the malfunctioning of cardiomyocytes and cardiofibroblasts in the course of MCD might be related to alterations in the iron homeostasis.

Rotational atherectomy (RA) is an established technique for modifying heavily calcified and fibrotic coronary artery lesions. Despite its efficacy, the use of a high-speed rotating burr can provoke platelet activation and endothelial injury, thereby increasing thrombotic risk, promoting inflammation, and impairing vascular healing. This study investigated the effects of RA and its procedural characteristics on endothelial function and platelet activation by assessing circulating biomarkers. We prospectively analyzed 34 patients undergoing elective RA at a tertiary center. Blood samples were obtained before and 12–24 h after the procedure. Plasma levels of soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), platelet factor 4 (PF4), P-selectin, and cluster of differentiation 40 ligand (CD40L) were measured. The study population had a mean age of 71 ± 8.9 years, and 73.8% were male. Cardiovascular comorbidities were prevalent, including diabetes (61.9%), hypertension (92.9%), hypercholesterolemia (42.9%), heart failure (45.2%), atrial fibrillation (21.4%), prior PCI (81%), and prior CABG (11.9%). RA significantly increased levels of P-selectin (55.5 ± 26.1 vs. 68.9 ± 26.5, p < 0.001), CD40L (2261.3 ± 2489.9 vs. 3602.0 ± 2428.5, p = 0.01), and PF4 (6054.7 ± 5751.8 vs. 10,877.6 ± 4979.7, p < 0.001). Moreover, mean burr speed correlated with CD40L elevation, while burr-to-artery ratio correlated with E-selectin increase (all p < 0.05). RA induces significant platelet activation and endothelial injury, with biomarker changes suggesting correlation with procedural parameters. These findings highlight the biological impact of RA and may inform strategies to optimize the safety of complex PCI.

Acute heart failure (AHF) causes abrupt hemodynamic disturbances, including reduced forward flow and venous congestion, which may extend beyond the heart and contribute to peripheral organ stress. Skeletal muscle may be particularly vulnerable to these changes, but the relationship between acute hemodynamic status and circulating markers of skeletal muscle stress and regulation remains unclear. We prospectively enrolled 35 men hospitalized with AHF and non-invasively assessed their cardiac index (CI) by impedance cardiography and right atrial pressure (RAP) by echocardiography. Plasma carbonic anhydrase III (CA3), creatine kinase-MM (CK-MM), lactate, myostatin, and follistatin were measured at admission, discharge, and 30 days after discharge. Patients were analyzed according to low CI, defined as CI < 2.2 L·min⁻¹·m⁻²; elevated RAP, defined as RAP ≥ 8 mmHg; and combined CI/RAP profiles. CA3 and CK-MM were higher in patients with low CI or elevated RAP and were highest in the low-CI/elevated-RAP profile. CA3 and lactate did not significantly change during follow-up, whereas CK-MM modestly increased at 30 days. Myostatin and follistatin were highest at admission and decreased after clinical stabilization. In this pilot cohort of men hospitalized with AHF, estimated lower perfusion and greater venous congestion were associated with higher circulating markers of skeletal muscle stress, while muscle regulatory myokines declined after stabilization. These findings suggest that skeletal muscle-related biomarkers may reflect peripheral consequences of acute hemodynamic disturbance in AHF and warrant further investigation in larger cohorts.