The lncRNA ADAMTS9-AS1/miR-185-5p/KAT7 ceRNA network inhibits cardiomyocyte hypertrophy in hypertrophic obstructive cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM) is a well-recognized inherited cardiac disease. This study was conducted to explore the role of lncRNA ADAMTS9 antisense RNA 1 (ADAMTS9-AS1) in HOCM-induced cardiomyocyte hypertrophy. The serum of HOCM patients was collected. AC16 cells were treated with isoproterenol (ISO) and transfected with oe-ADAMTS9-AS1 vector, miR-185-5p mimic, and lysine acetyltransferase 7 (KAT7) specific small interfering RNA. lncRNA ADAMTS9-AS1, miR-185-5p, KAT7, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in the serum or cells were determine by qRT-PCR or Western blot assay. Cell surface area was observed by Texas Red-Phalloidin staining. Subcellular localization of lncRNA ADAMTS9-AS1 was tested by nuclear/cytoplasmic fractionation assay, with RNA pull-down and dual-luciferase assay to validate gene interactions. lncRNA ADAMTS9-AS1 was downregulated in the serum of HOCM patients and ISO-treated AC16 cells. lncRNA ADAMTS9-AS1 overexpression inhibited ISO-induced cardiomyocyte hypertrophy and reduced levels of ANP and BNP. lncRNA ADAMTS9- AS1 was located in cytoplasm and inhibited miR-185-5p expression through targeted binding. miR-185-5p bound to KAT7 3'UTR and inhibited KAT7 expression. miR-185-5p overexpression and KAT7 knockdown both neutralized the inhibitory role of lncRNA ADAMTS9-AS1 in cardiomyocyte hypertrophy. Overall, lncRNA ADAMTS9-AS competitively bound to miR-185-5p to up-regulate KAT7 and thus inhibited cardiomyocyte hypertrophy.

Differential Expression of LOXL1-AS1 in Coronary Heart Disease and its Regulatory Mechanism in ox-LDL-Induced Human Coronary Artery Endothelial Cell Pyroptosis.

OBJECTIVE: Coronary heart disease (CHD) is a notable contributor to the burden of human health. Dysregulated long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of CHD. This study investigated the expression pattern of lncRNA LOXL1-AS1 in CHD and its regulatory mechanism in oxidized low-density lipoprotein (ox-LDL)-induced human coronary artery endothelial cell (HCAEC) pyroptosis. METHODS: Serum was collected from 62 CHD patients and 62 healthy volunteers for the detection of LOXL1-AS1 expression. The value of LOXL1-AS1 in CHD diagnosis and major cardiovascular adverse event (MACE) prediction was analyzed using the ROC curve. LOXL1-AS1, miR-16-5p, and SNX16 expressions in ox-LDL-treated HCAECs were determined using RT-qPCR. NLPR3, cleaved-caspase-1, and GSDMD-N protein levels were measured using Western blot. IL-1ß and IL-18 concentrations were measured using ELISA. The binding relationships between LOXL1-AS1 and miR-16-5p and miR-16-5p and SNX16 were verified. Functional rescue experiment was performed to verify the role of miR-16-5p in HCAEC pyroptosis. RESULTS: LOXL1-AS1 was highly expressed in CHD patients. LOXL1-AS1 had diagnostic value for CHD and predictive value for MACE occurrence. ox-LDL-treated HCAECs showed reduced viability, increased IL-1ß and IL-18 concentrations, and elevated NLPR3, cleaved-caspase-1, and GSDMD-N levels. LOXL1-AS1 silencing promoted cell viability and reduced pyroptosis. LOXL1-AS1 bound to miR-16-5p and miR-16-5p targeted SNX16. Inhibition of miR-16-5p reversed the inhibitory effect of LOXL1-AS1 silencing on HCAEC pyroptosis. CONCLUSION: LOXL1-AS1 was elevated in CHD patients with a good diagnostic value for CHD and predictive value for MACE. LOXL1-AS1 downregulated miR-16-5p expression by binding to miR-16-5p to enhance ox-LDL-induced HCAEC pyroptosis, which may be associated with upregulation of SNX16 transcription.

Relation of quantitative flow ratio with transit time coronary artery bypass graft flow measurement.

Background: Quantitative flow ratio (QFR) is a new functional index to assess the functional significance of coronary stenosis. While whether there is an association between QFR and transit-time flow measurement (TTFM) parameters of the target coronary artery has not been well addressed. Methods: A total of 89 patients receiving the in situ left internal thoracic artery (LITA) grafts to the left anterior descending artery (LAD), and 19 patients undergoing the saphenous vein grafts (SVG) were enrolled in this retrospective study. The QFR value of the LAD was evaluated preoperatively. According to the QFR values, patients with the LITA to the LAD bypass grafts were divided into two groups (group A1: QFR < 0.75, group A2: QFR ≥ 0.75), and SVG patients were divided into two groups (V1 group: QFR < 0.75, V2 group: QFR ≥ 0.75). Results: In groups A1 and A2, respectively, median graft flow (Qm) was 44 (34) mL/minute and 26.5 (30.0) ml/minute; median pulsatility index (PI) was 2.00 (1.00) and 2.65 (0.90). Significant differences were observed in Qm (P = 0.034) and PI (P = 0.030). And the correlation coefficients of the TTFM variables with QFR were Qm: r = r = -0.226, (P = 0.036), PI: r = 0.265 (P = 0.012) among the LITA to LAD population. Conclusion: TTFM variables, especially the PI, of the LITA in situ graft to the LAD during Coronary artery bypass grafting (CABG) are strongly affected by preoperative QFR values. Moreover, in functionally mild coronary stenosis, the chance of competitive flow increases.

Mirabegron Ameliorated Atherosclerosis of ApoE-/- Mice in Chronic Intermittent Hypoxia but Not in Normoxia.

PURPOSE: It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates ß3 adrenergic receptor (ß3 AR). However, the effect of selective ß3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. METHODS: We generated a CIH-induced atherosclerosis model through exposing ApoE-/- mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5-21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective ß3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. RESULTS: The expression of ß3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE-/- mice in CIH but not in normoxia. Mechanistically, mirabegron activated ß3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, ß3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. CONCLUSION: This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via ß3 AR-mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.

Development and Validation of a Novel Nomogram for Preoperative Prediction of In-Hospital Mortality After Coronary Artery Bypass Grafting Surgery in Heart Failure With Reduced Ejection Fraction.

Background and Aims: Patients with heart failure with reduced ejection fraction (HFrEF) are among the most challenging patients undergoing coronary artery bypass grafting surgery (CABG). Several surgical risk scores are commonly used to predict the risk in patients undergoing CABG. However, these risk scores do not specifically target HFrEF patients. We aim to develop and validate a new nomogram score to predict the risk of in-hospital mortality among HFrEF patients after CABG. Methods: The study retrospectively enrolled 489 patients who had HFrEF and underwent CABG. The outcome was postoperative in-hospital death. About 70% (n = 342) of the patients were randomly constituted a training cohort and the rest (n = 147) made a validation cohort. A multivariable logistic regression model was derived from the training cohort and presented as a nomogram to predict postoperative mortality in patients with HFrEF. The model performance was assessed in terms of discrimination and calibration. Besides, we compared the model with EuroSCORE-2 in terms of discrimination and calibration. Results: Postoperative death occurred in 26 (7.6%) out of 342 patients in the training cohort, and in 10 (6.8%) out of 147 patients in the validation cohort. Eight preoperative factors were associated with postoperative death, including age, critical state, recent myocardial infarction, stroke, left ventricular ejection fraction (LVEF) ≤35%, LV dilatation, increased serum creatinine, and combined surgery. The nomogram achieved good discrimination with C-indexes of 0.889 (95%CI, 0.839-0.938) and 0.899 (95%CI, 0.835-0.963) in predicting the risk of mortality after CABG in the training and validation cohorts, respectively, and showed well-fitted calibration curves in the patients whose predicted mortality probabilities were below 40%. Compared with EuroSCORE-2, the nomogram had significantly higher C-indexes in the training cohort (0.889 vs. 0.762, p = 0.005) as well as the validation cohort (0.899 vs. 0.816, p = 0.039). Besides, the nomogram had better calibration and reclassification than EuroSCORE-2 both in the training and validation cohort. The EuroSCORE-2 underestimated postoperative mortality risk, especially in high-risk patients. Conclusions: The nomogram provides an optimal preoperative estimation of mortality risk after CABG in patients with HFrEF and has the potential to facilitate identifying HFrEF patients at high risk of in-hospital mortality.

The role and the signal pathways of Yes-associated protein 2 in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous myocardial disease characterized by myocardial hypertrophy, myocardial mechanical and electrical activity obstacles. This study aimed to explore the relationship between YAP2 (Yes-associated protein 2) and HCM and clarify a signaling path about the pathogenesis of HCM. Our study confirms that YAP2 can promote myocardial cell hypertrophy at the molecular level (myocardial lineage cell H9C2), organ level (clinical specimens of human HCM), and an animal model (a mouse model of HCM with cardiac-specific transgenic and knockout YAP2). The detailed molecular mechanisms linking YAP2 to cardiomyocyte hypertrophy and HCM were investigated. This study proved that YAP2, as the final reaction factor in Hippo pathways, influences Akt1 activity to affect the downstream genes, which participate in the formation of HCM by promoting myocardial cell proliferation and cardiac hypertrophy.

Analysis of risk factors of low cardiac output syndrome after congenital heart disease operation: what can we do.

BACKGROUND: It's necessary to analyze the related risk factors and complications of low cardiac output syndrome (LCOS) after operation in children with congenital heart disease (CHD), to elucidate the management strategy of LCOS. METHODS: CHD children admitted to the department of cardiology in our hospital from January 15, 2019 to October 31, 2020 were included. The personal and clinical data of CHD children with LCOS and without LCOS were collected and compared. Logistic regression analyses were conducted to identify the risk factors of postoperative LCOS. Besides, the complication and mortality of LCOS and no LCOS patients were compared. RESULTS: A total of 283 CHD patients were included, the incidence of postoperative LCOS in CHD patients was 12.37%. There were significant differences in the age, preoperative oxygen saturation, two-way ventricular shunt, duration of CPB and postoperative residual shunt between two groups (all p < 0.05). Logistic regression analyses indicated that age ≤ 4y(OR2.426, 95%CI1.044 ~ 4.149), preoperative oxygen saturation ≤ 93%(OR2.175, 95%CI1.182 ~ 5.033), two-way ventricular shunt (OR3.994, 95%CI1.247 ~ 6.797), duration of CPB ≥ 60 min(OR2.172, 95%CI1.002 ~ 4.309), postoperative residual shunt (OR1.487, 95%CI1.093 ~ 2.383) were the independent risk factors of LCOS in patients with CHD (all p < 0.05). There were significant differences in the acute liver injury, acute kidney injury, pulmonary infection, tracheotomy, duration of mechanical ventilation, length of ICU stay and mortality (all p < 0.05), no significant difference in the 24 h drainage was found(p = 0.095). CONCLUSION: LCOS after CHD is common, more attentions should be paid to those patients with age ≤ 4y, preoperative oxygen saturation ≤ 93%, two-way ventricular shunt, duration of CPB ≥ 60 min, postoperative residual shunt to improve the prognosis of CHD patients.

Identification of candidate genes in ischemic cardiomyopathy by gene expression omnibus database.

BACKGROUND: Ischemic cardiomyopathy (ICM) is one of the most usual causes of death worldwide. This study aimed to find the candidate gene for ICM. METHODS: We studied differentially expressed genes (DEGs) in ICM compared to healthy control. According to these DEGs, we carried out the functional annotation, protein-protein interaction (PPI) network and transcriptional regulatory network constructions. The expression of selected candidate genes were confirmed using a published dataset and Quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: From three Gene Expression Omnibus (GEO) datasets, we acquired 1081 DEGs (578 up-regulated and 503 down-regulated genes) between ICM and healthy control. The functional annotation analysis revealed that cardiac muscle contraction, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy were significantly enriched pathways in ICM. SNRPB, BLM, RRS1, CDK2, BCL6, BCL2L1, FKBP5, IPO7, TUBB4B and ATP1A1 were considered the hub proteins. PALLD, THBS4, ATP1A1, NFASC, FKBP5, ECM2 and BCL2L1 were top six transcription factors (TFs) with the most downstream genes. The expression of 6 DEGs (MYH6, THBS4, BCL6, BLM, IPO7 and SERPINA3) were consistent with our integration analysis and GSE116250 validation results. CONCLUSIONS: The candidate DEGs and TFs may be related to the ICM process. This study provided novel perspective for understanding mechanism and exploiting new therapeutic means for ICM.

Soluble ST2, Galectin-3 and clinical prognosis of patients with hypertrophic cardiomyopathy undergoing ventricular septal myectomy: a correlation analysis.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common chromosomal abnormal heart disease. The pathophysiological mechanism of HCM is complex. Several studies have suggested that the level of Soluble ST2 (sST2) may be a biomarker of chronic systolic heart failure, however, the role of sST2 in HCM remains unclear. So we performed this study to analyze the role of Soluble ST2 (sST2), Galectin-3 (Gal-3) and its correlations with clinical prognosis of patients with hypertrophic cardiomyopathy (HCM) undergoing ventricular septal myectomy. METHODS: HCM patients who underwent modified Morrow surgery in our hospital during June 2016-June 2018 were included. We divided the patients into different groups stratified by sST2 and Gal-3 level. Besides, we included volunteers without heart disease for medical examination as normal controls. Biochemical analyses were conducted to identify the biomarkers difference. The predictive value of sST2 and Gal-3 on all-cause mortality was evaluated with Cox regression analysis. RESULTS: A total of 125 HCM patients were included in this present study. The sST2 and Gal-3 levels in HCM patients were significantly higher than that in control group (all P<0.001); there were significant differences in the incidence of all-cause mortality for HCM patients stratified by the sST2 and Gal-3 level; Cox univariate regression survival analysis showed that the hypertension (HR =1.19, 95% CI: 1.01-1.38), maximum wall thickness (HR =1.48, 95% CI: 1.04-1.98), Log sST2 (HR =1.02, 95% CI: 1.01-1.05), Log Gal-3 (HR =1.17, 95% CI: 1.09-1.32) were the predictors for all-cause mortality in patients with HCM, and Cox multivariate risk regression showed that maximum wall thickness was the independent predictors of all-cause mortality in patients with HCM (HR =1.63, 95% CI: 1.35-1.97). CONCLUSIONS: Even through sST2 and Gal-3 were not associated with clinical prognosis of patients with HCM undergoing ventricular septal myectomy, it may be involved in the progress of HCM, more studies are warranted to identify the potential mechanism and reverence value.

Atorvastatin reverses the dysfunction of human umbilical vein endothelial cells induced by angiotensin II.

Statins exert pleiotropic effects on endothelial cells, in addition to lowering cholesterol. This study evaluated angiotensin II (Ang II)-induced dysfunction in human umbilical vein endothelial cells (HUVECs), and the effects of atorvastatin (Ator) on induced HUVECs in vitro. The cytotoxicity of Ang II and Ator was determined by the MTT assay. A series of cellular responses were screened, including oxidative stress, cellular apoptosis, inflammatory response, autophagy, expression of endothelial nitric oxide synthase and the angiogenic function of HUVECs. Ator returned these cellular responses to a normal level. The present study also examined cellular organelle dysfunction. In HUVECs, Ang II triggered mitochondrial damage, as demonstrated by a decreased mitochondrial membrane potential, while Ator attenuated this Ang II-induced damage. The observed cellular dysfunction may cause endothelial senescence due to excessive cell injury. The current study examined several aging markers, which revealed that these disorders of cellular functions triggered endothelial senescence, which was delayed by Ator. Ator also suppressed Ang II-induced angiogenesis damage. The data presented in this study strongly suggested that Ang II induced a series of processes that lead to cellular dysfunction in HUVECs, including oxidative stress, inflammation, and mitochondrial damage, leading to apoptosis and endothelial senescence. However, Ator significantly reversed these effects and modulated intracellular stability. The present study indicated that Ator serves an antagonistic role against HUVEC dysfunction and may potentially prevent several diseases, including coronary disease and atherosclerosis, by maintaining cellular homeostasis.

[Distribution and antibiotics resistance related to nosocomial pathogenic bacteria infection in patients after cardiac surgery].

OBJECTIVE: To investigate the clinical distribution and antibiotics resistance of nosocomial infection caused pathogenic bacteria in patients after cardiac surgery. METHODS: Clinical data from 612 patients after cardiac surgery under microbiologically documented nosocomial infection was retrospectively analyzed from January 2007 to December 2012. Identification on related bacterial was performed in an automatic ATB Expression system while antimicrobial susceptibility was tested by Kirby-Bauer method. RESULTS: were analyzed by WHONET5.4. RESULTS: There were 697 strains of clinical pathogenic bacilli isolates identified and 421 (60.4%) of them were isolated from sputum while 185 (26.5%) were from blood. Acinetobacter spp. (124 strains, 17.8%), Pseudomonas aeruginosa (85 strains, 12.2%) and Klebsiella pneumoniae (50 strains, 7.2%) were the predominant Gram-negative bacilli while S. epidermidis (75 strains, 10.8%) was the predominant Gram-positive cocci. The predominant eumycete was Candida albicans (43 strains, 6.2%). RESULTS: from the susceptibility test showed that carbapenems, cefoperazone/sulbactam and piperacillin/tazobactam were the most active antibiotics. The detection of meticillin-resistant Staphylococcus (MRS) were 82.9% in S aureus and 95.9% in coagulase negative Staphylococcus. There was no Staphylococcus strains resistant to vancomycin found. CONCLUSION: Non-fermenting Gram-negative bacilli and Staphylococcus appeared the important pathogens in patients after cardiac surgery. Drug resistance to antibiotics was quite common. Prevention on nosocomial infection and rational use of antibiotics remained very important in reducing the amount of drug resistant strains.