Limited microRNAs (miRNAs, miRs) have been reported to be necessary for exercise-induced cardiac growth and essential for protection against pathological cardiac remodeling. Here we determined members of the miR-17-92 cluster and their passenger miRNAs expressions in two distinct murine exercise models and found that miR-17-3p was increased in both. miR-17-3p promoted cardiomyocyte hypertrophy, proliferation, and survival. TIMP-3 was identified as a direct target gene of miR-17-3p whereas PTEN was indirectly inhibited by miR-17-3p. Inhibition of miR-17-3p in vivo attenuated exercise-induced cardiac growth including cardiomyocyte hypertrophy and expression of markers of myocyte proliferation. Importantly, mice injected with miR-17-3p agomir were protected from adverse remodeling after cardiac ischemia/reperfusion injury. Collectively, these data suggest that miR-17-3p contributes to exercise-induced cardiac growth and protects against adverse ventricular remodeling. miR-17-3p may represent a novel therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.

Acute myocardial infraction is the most severe type of coronary artery disease and remains a substantial burden to the health care system globally. Although myocardial reperfusion is critical for ischemic cardiac tissue survival, the reperfusion itself could cause paradoxical injury. This paradoxical phenomenon is known as ischemia–reperfusion injury (IRI), and the exact molecular mechanism of IRI is still far from being elucidated and is a topic of controversy. Meanwhile, ferroptosis is a nonapoptotic form of cell death that has been reported to be associated with various cardiovascular diseases. Thus, we explored the potential ferroptosis mechanism and target in cardiac IRI via bioinformatics analysis and experiment. GSE4105 data were obtained from the GEO database and consist of a rat IRI model and control. After identifying differentially expressed ferroptosis-related genes (DEFRGs) and hub genes of cardiac IRI, we performed enrichment analysis, coexpression analysis, drug–gene interaction prediction, and mRNA–miRNA regulatory network construction. Moreover, we validated and explored the multitemporal expression of hub genes in a hypoxia/reoxygenation (H/R)-induced H9C2 cell injury model under different conditions via RT-qPCR. A total of 43 DEFRGs and 7 hub genes (tumor protein p53 [Tp53], tumor necrosis factor [Tnf], hypoxia-inducible factor 1 subunit alpha [Hif1a], interleukin 6 [Il6], heme oxygenase 1 [Hmox1], X-box binding protein 1 [Xbp1], and caspase 8 [Casp8]) were screened based on bioinformatics analysis. The functional annotation of these genes revealed apoptosis, and the related signaling pathways could have association with the pathogenesis of ferroptosis in cardiac IRI. In addition, the expression of the seven hub genes in IRI models were found higher than that of control under different H/R conditions and time points. In conclusion, the analysis of 43 DEFRGs and 7 hub genes could reveal the potential biological pathway and mechanism of ferroptosis in cardiac IRI. In addition, the multitemporal expression change of hub genes in H9C2 cells under different H/R conditions could provide clues for further ferroptosis mechanism exploring, and the seven hub genes could be potential biomarkers or therapeutic targets in cardiac IRI.

Objectives: To identify risk factors associated with cardiac valve calcification that is easily detectable through routine blood tests in patients who received valve replacement therapy. Methods: Four hundred patients with valvular heart disease who underwent valve replacement surgery between December 2009 and January 2013 were enrolled in this study. Of these, 77 had valve calcification; the other 323 did not. Multivariate logistic regression analysis was used to assess for risk factors associated with valve calcification. Results: In our study population, rheumatic valve lesions were the most common reason for valve replacement. Degenerative nonstenotic valve lesion was a protective factor and degenerative stenotic valve lesion was a strong risk factor for valve calcification. Serum levels of gamma-glutamyl transferase (GGT) of between 30 and 46 IU/l and >90 IU/l and total bilirubin (TBIL) of between 15 and 20 μmol/l were positively correlated with valve calcification. Meanwhile, serum calcium (Ca²⁺) levels of between 2.3 and 2.4 mmol/l were negatively correlated with rheumatic valve calcification. Conclusions: Degenerative stenotic lesion is a risk factor and degenerative nonstenotic lesion a protective factor for cardiac valve calcification. Serum GGT and TBIL levels are positively correlated and serum Ca²⁺ levels negatively correlated with rheumatic cardiac valve calcification.

Murine P19 embryonal carcinoma cells are multipotent cells that can differentiate into cardiomyocytes when treated with dimethyl sulfoxide. This experimental model provides an invaluable tool to study different aspects of cardiac differentiation, such as the function of cardiac‑specific transcription factors and signaling pathways, and the regulation of contractile protein expression. The role of mitochondria during cardiac differentiation is unclear. In this context, we have examined the mitochondrial-related changes in undifferentiated and differentiated P19 cells. We observed that mitochondrial DNA content sharply decreased in P19 cell aggregates compared to undifferentiated cells, accompanied by decreased levels of adenosine triphosphate (ATP) and reactive oxygen species (ROS). Following the aggregation stage, the mitochondrial DNA content reached its highest level on day 7 of the differentiation process, with the intracellular ROS level showing a trend to increase, similar to cellular ATP production. In conclusion, our study on differentiating P19 embryonal carcinoma cells provides new insights into the role of mitochondria in the differentiation of P19 stem cells into beating cardiomyocytes.