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Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome that is extremely difficult to manage, and there is currently no effective treatment. We want to elucidate the therapeutic effect of ethyl pyruvate (EP) on PAH and its possible mechanism. Pulmonary artery endothelial cells (PAECs) were cultured in conventional low-oxygen environments, and cellular proliferation was monitored after treatment with EP. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 was detected by Western blot. After hyperkinetic PAH rabbits' models were treated with EP, hemodynamic data were collected. Right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 protein was also detected after using autophagy inhibitor and agonists. We found that EP could inhibit PAECs proliferation. After EP treatment, expression of p-PI3K/Akt was upregulated in vitro and in vivo. LC3-II and Beclin-1 were inhibited and their expression was lower after autophagy inhibitor was given, while after administration of autophagy agonists, their expression was higher than that in the EP alone group. Besides, EP attenuated PAH, and right ventricular hypertrophy and pulmonary vascular remodeling were also reversed. EP can reduce PAH and reverse vascular remodeling which is associated with inhibition of autophagy in PAECs based on PI3K-Akt signaling pathway. The results of this study can provide surgical opportunities for patients with severe PAH caused by congenital heart disease in clinical cardiovascular surgery.

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AIM: Hyperkinetic pulmonary arterial hypertension (PAH) is a complication of congenital heart disease. Gene therapy is a new experimental treatment for PAH, and ultrasound-mediated gene-carrying microbubble targeted delivery is a promising development for gene transfer. METHODS: This study successfully established a hyperkinetic PAH rabbit model by a common carotid artery and jugular vein shunt using the cuff style method. Liposome microbubbles carrying the hepatocyte growth factor (HGF) gene were successfully constructed. An in vitro experiment evaluated the appropriate intensity of ultrasonic radiation by Western blots and 3H-TdR incorporation assays. In an in vivo experiment, after transfection of ultrasound-mediated HGF gene microbubbles, catheterisation was applied to collect haemodynamic data. Hypertrophy of the right ventricle was evaluated by measuring the right ventricle hypertrophy index. Western blot and immunohistochemistry analyses were used to detect the expression of human (h)HGF and angiogenic effects, respectively. RESULTS: The most appropriate ultrasonic radiation intensity was 1.0 W/cm2 for 5 minutes. Two weeks after transfection, both systolic pulmonary arterial pressure and mean pulmonary arterial pressure were attenuated. Hypertrophy of the right ventricle was reversed. hHGF was transplanted into the rabbits, resulting in a high expression of hHGF protein and an increase in the number of small pulmonary arteries. Ultrasound-mediated HGF gene microbubble therapy was more effective at attenuating PAH and increasing the density of small pulmonary arteries than single HGF plasmid transfection. CONCLUSIONS: Ultrasound-mediated HGF gene microbubbles significantly improved the target of gene therapy in a rabbit PAH model and enhanced the tropism and transfection rates. Thus, the technique can effectively promote small pulmonary angiogenesis and play a role in the treatment of PAH without adverse reactions.

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Background: Myocardial infarction (MI) is a common cardiac condition with a high incidence of morbidity and mortality. Despite extensive medical treatment for MI, the development and outcomes of post-MI heart failure (HF) continue to be major factors contributing to poor post-MI prognosis. Currently, there are few predictors of post-MI heart failure. Methods: In this study, we re-examined single-cell RNA sequencing and bulk RNA sequencing datasets derived from the peripheral blood samples of patients with myocardial infarction, including patients who developed heart failure and those who did not develop heart failure after myocardial infarction. Using marker genes of the relevant cell subtypes, a signature was generated and validated using relevant bulk datasets and human blood samples. Results: We identified a subtype of immune-activated B cells that distinguished post-MI HF patients from non-HF patients. Polymerase chain reaction was used to confirm these findings in independent cohorts. By combining the specific marker genes of B cell subtypes, we developed a prediction model of 13 markers that can predict the risk of HF in patients after myocardial infarction, providing new ideas and tools for clinical diagnosis and treatment. Conclusion: Sub-cluster B cells may play a significant role in post-MI HF. We found that the STING1, HSPB1, CCL5, ACTN1, and ITGB2 genes in patients with post-MI HF showed the same trend of increase as those without post-MI HF.

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Background: Ischemic cardiomyopathy (ICM) induced heart failure (HF) is one of the most common causes of death worldwide. This study aimed to find candidate genes for ICM-HF and to identify relevant biomarkers by machine learning (ML). Methods: The expression data of ICM-HF and normal samples were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ICM-HF and normal group were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and gene ontology (GO) annotation analysis, protein-protein interaction (PPI) network, gene pathway enrichment analysis (GSEA), and single-sample gene set enrichment analysis (ssGSEA) were performed. Weighted gene co-expression network analysis (WGCNA) was applied to screen for disease-associated modules, and relevant genes were derived using four ML algorithms. The diagnostic values of candidate genes were assessed using receiver operating characteristic (ROC) curves. The immune cell infiltration analysis was performed between the ICM-HF and normal group. Validation was performed using another gene set. Results: A total of 313 DEGs were identified between ICM-HF and normal group of GSE57345, which were mainly enriched in biological processes and pathways related to cell cycle regulation, lipid metabolism pathways, immune response pathways, and intrinsic organelle damage regulation. GSEA results showed positive correlations with pathways such as cholesterol metabolism in the ICM-HF group compared to normal group and lipid metabolism in adipocytes. GSEA results also showed a positive correlation with pathways such as cholesterol metabolism and a negative correlation with pathways such as lipolytic presentation in adipocytes compared to normal group. Combining multiple ML and cytohubba algorithms yielded 11 relevant genes. After validation using the GSE42955 validation sets, the 7 genes obtained by the machine learning algorithm were well verified. The immune cell infiltration analysis showed significant differences in mast cells, plasma cells, naive B cells, and NK cells. Conclusion: Combined analysis using WGCNA and ML identified coiled-coil-helix-coiled-coil-helix domain containing 4 (CHCHD4), transmembrane protein 53 (TMEM53), acid phosphatase 3 (ACPP), aminoadipate-semialdehyde dehydrogenase (AASDH), purinergic receptor P2Y1 (P2RY1), caspase 3 (CASP3) and aquaporin 7 (AQP7) as potential biomarkers of ICM-HF. ICM-HF may be closely related to pathways such as mitochondrial damage and disorders of lipid metabolism, while the infiltration of multiple immune cells was identified to play a critical role in the progression of the disease.

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A 37-year-old male patient with corrected transposition of great arteries (ccTGA) with cor triatriatum sinister (CTS), left superior vena cava, and atrial septal defects is reported in our case. None of these impacted the patient's growth or development, nor daily work until age 33. Later, the patient developed symptoms of obvious impaired heart function, which improved after medical treatment. However, the symptoms reappeared and gradually worsened two years later, and we decided to treat it with surgery. In this case, we selected tricuspid mechanical valve replacement, cor triatriatum correction, and atrial septal defect repair. During the follow-up of five years, the patient had no obvious symptoms, ECG did not change significantly from five years ago, and the cardiac color Doppler ultrasound showed RVEF 0.51.

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Over the years, bioinformatics tools have been used to identify functional genes. In the present study, bioinformatics analyses were conducted to explore the underlying molecular mechanisms of angiogenic factors in calcific aortic valve disease (CAVD). The raw gene expression profiles were from datasets GSE153555, GSE83453, and GSE51472, and the angiogenesis-related gene set was from the Gene Set Enrichment Analysis database (GSEA). In this study, R was used to screen for differentially expressed genes (DEGs) and co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) Pathway enrichment analysis were performed on DEGs and validated in clinical samples. DEGs in CAVD were significantly enriched in numerous immune response pathways, inflammatory response pathways and angiogenesis-related pathways. Nine highly expressed angiogenesis-related genes were identified, of which secretogranin II (SCG2) was the most critical gene. MiRNA and transcription factors (TFs) networks were established centered on five DEGs, and zinc finger E-box binding homeobox 1 (ZEB1) was the most important transcription factor, verified by PCR, immunohistochemical staining and western blotting experiments. Overall, this study identified key genes and TFs that may be involved in the pathogenesis of CAVD and may have promising applications in the treatment of CAVD.

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INTRODUCTION: CT imaging analysis of mitral annulus (MA), coronary sinus (CS) and left circumflex artery (LCX) is critical to transcatheter mitral annuloplasty (TMA), which, however, is scantly reported. We aimed to comprehensively assess MA, CS and LCX anatomy and geometry in mitral regurgitation (MR) based on 3-D reconstruction of cardiac CT images. METHODS: Patients with primary or secondary MR and patients without MR were recruited and underwent cardiac CT examination. MR severity was evaluated by echocardiography. 3-D reconstruction of cardiac CT images was done by the Mimics Research 21.0 software. A MA-centered two dimensional coordinate system, a CS plane, a MA plane and a series of auxiliary planes along the posterior MA were created for the measurement of parameters defining MA, CS and LCX anatomy and geometry during the cardiac cycle. RESULTS: The secondary MR group had a significantly higher MA perimeter index than the other two groups during the cardiac cycle. The CS diameters at most sites, and the posterior MA radian were substantially greater in the two MR groups. Distances between the CS and MA at some locations were significant different among the three groups. The secondary MR group had a significantly smaller CS-MA plane angle than the other two groups during systole, and than control group during diastole. The site where the CS crossed LCX was pinpointed. CONCLUSION: The comprehensive information from this study may help improve the results of TMA and enhance the design of devices for a better annuloplasty effect.

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BACKGROUND: Hypertrophic cardiomyopathy is a commonly inherited heart disease. In addition, single coronary artery (SCA) is a rare congenital anomaly of the coronary arteries. And SCA concomitant with severe hypertrophic obstructive cardiomyopathy (HOCM) has seldom been reported in the literature. However, such cases have not been reported to be treated with the Morrow procedure. CASE PRESENTATION: Herein, we presented a case of a 64-year-old female diagnosed with a single left coronary artery with severe HOCM. The HOCM was treated with the Morrow procedure. The patient was discharged on the seventh postoperative day and was asymptomatic during the follow-up. CONCLUSION: To our knowledge, this is the first study reporting a single left coronary artery with severe HOCM treated with the Morrow procedure. In addition, myocardial protection by cardioplegia antegrade perfusion was safe for the patient with SCA and HOCM.

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