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Hypoxia‐induced apoptosis is linked to the pathogenesis of myocardial infarction (MI) and heart failure. Ubiquitin‐specific peptidase 7 (USP7) is related to catabolic/pro‐apoptotic signaling. However, its role in cardiomyocyte injury is unclear. In this study, we aimed to investigate the role and the underlying regulatory mechanism of USP7 in MI. H9c2 cardiomyocytes were cultured in hypoxia to establish an in vitro model of myocardial hypoxic/ischemic injury. Sprague‐Dawley (SD) rats were used to establish animal models with MI. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot assays were performed to evaluate the expression levels of miR‐409‐5p, USP7, and p53, respectively. After USP7 and miR‐409‐5p were selectively regulated in H9c2 cells, the inflammatory response, apoptosis, and cell viability were detected by ELISA, flow cytometry, and MTT assay, respectively. The interaction between USP7 and miR‐409‐5p was determined by bioinformatics analysis, qRT‐PCR, Western blot, and dual‐luciferase reporter assay. LVEF, LVIDd, and LVIDs of rats after MI were also measured. USP7 expression was markedly elevated while miR‐409‐5p expression was significantly down‐regulated in H9c2 cells under hypoxic culture. Augmentation of USP7 expression led to a dramatic promotion of hypoxia‐induced apoptosis of cardiomyocytes, accompanied by an increase in the secretion of the cytokines IL‐1β, TNF‐α, and IL‐6. Myocardial injury markers LDH, cTnI, and CK‐MB expressions were also increased. Besides, overexpression of USP7 aggravated left ventricular remodeling and decreased left ventricular function of the rats. Conversely, the up‐regulation of miR‐409‐5p expression protected H9c2 cells from apoptosis and inhibited the release of cytokines and myocardial injury. Left ventricular remodeling and left ventricular function were also improved by miR‐409‐5p overexpression. Furthermore, USP7 was identified as a target of miR‐409‐5p and the overexpression of miR‐409‐5p reversed the effects of USP7 on H9c2 cells. USP7 exacerbates myocardial ischemic injury by promoting inflammation and apoptosis of cardiomyocytes, and the up‐regulation of its expression is partly caused by the down‐regulation of miR‐409‐5p expression. [ABSTRACT FROM AUTHOR]

Oxidative stress plays an important role in the progression of cardiac diseases, including ischemia/reperfusion injury, myocardial infarction, and heart failure. Growing evidence indicates that cabbage has various pharmacological properties against a wide range of diseases, such as cardiovascular diseases, hepatic diseases, and cancer. However, little is known about its effects on oxidative stress in cardiomyocytes or the underlying mechanisms. Therefore, the present study examined the effects of cabbage extract on oxidative stress in H9c2 cardiomyoblasts. Cell viability, reactive oxygen species (ROS) production, apoptosis, mitochondrial functions, and expression levels of mitogen-activated protein kinase (MAPK) proteins were analyzed to elucidate the antioxidant effects of this extract. Cabbage extract protected against H2O2-induced cell death and did not elicit any cytotoxic effects. In addition, cabbage extract suppressed ROS production and increased expression of antioxidant proteins (SOD-1, catalase, and GPx). Cabbage extract also inhibited apoptotic responses and activation of MAPK proteins (ERK1/2, JNK, and p-38) in oxidative stress-exposed H9c2 cells. Notably, cabbage extract preserved mitochondrial functions upon oxidative stress. These findings reveal that cabbage extract protects against oxidative stress and suggest that it can be used as an alternative therapeutic strategy to prevent the oxidative stress in the heart. [ABSTRACT FROM AUTHOR]

Background: Speckle tracking-derived global longitudinal strain (GLS) of left ventricle is a potent prognostic marker for patients with ST-segment elevation myocardial infarction (STEMI). The purpose of this study was to investigate the difference of prognostic impact of GLS between anterior and nonanterior myocardial infarction. Methods: This study included 686 patients who underwent primary percutaneous coronary intervention for their first STEMI between November 2007 and April 2012. Differences in the prognostic impact of GLS between anterior MI group and nonanterior MI group were evaluated. The composite of all-cause mortality and hospitalization for heart failure in 2 years was investigated for outcome. Results: During the follow-up period, 77 (11.2%) adverse events occurred. The anterior and nonanterior MI groups included 339 and 347 patients, respectively. Among patients with anterior MI, GLS significantly predicted 2-year outcome in an adjusted model (adjusted hazard ratio [HR] 1.186; 95% confidence interval [CI] 1.071-1.314, P = 0.001), whereas the association between GLS and mortality was weaker in the nonanterior MI group (adjusted HR 0.977; 95% CI 0.884-1.081, P = 0.657). The interaction between the infarction territory and GLS was significant (P for interaction = 0.018), indicating that GLS was a more sensitive predictor of mortality in patients with anterior MI than that in those with nonanterior MI. Conclusions: Speckle tracking-derived GLS of left ventricle more sensitively predicted clinical outcome in patients with anterior MI than in those with nonanterior MI. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between country of birth and the utilization of coronary angiography, percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) after a first-time myocardial infarction (MI). Design, setting and patients: 117 494 MI patients of all ages who were admitted to coronary care units between 2001 and 2009 in Sweden were followed-up for three months after admission. Main outcome measures: Undergoing coronary angiography, PCI or CABG after first-time MI. Results: proportion of patients undergoing angiography and PCI increased whereas proportion of patients undergoing CABG also delay time for all three procedures decreased over the study period. The proportion of women undergoing any of the three procedures was markedly lower and delay time longer than those of men regardless of study period and migration background. Overall foreign-born first MI patients had higher rate of angiography (HR = 1.30, 95% CI: 1.27-1.33), PCI (HR = 1.27, 95% CI: 1.24-1.30) and CABG (HR = 1.21, 95% CI: 1.15-1.28) compared with Sweden born first MI patients. After controlling for potential confounding factors in multivariable models, the overall differences vanished for angiography and reduced markedly for PCI and CABG. However, multivariable stratified analysis by specific country of birth yielded higher rate of angiography among men born in Uganda (HR = 2.11, 95% CI: 1.00-4.43) and Peru (HR = 1.98, 95% CI: 1.07-3.68) and lower rate among men born in Croatia (HR = 0.71, 95% CI: 0.52-0.99) and women born in Thailand (HR = 0.49, 95% CI: 0.35-0.94). PCI adjusted rates were higher among women born in Palestine state (HR = 2.44, 95% CI: 1.15-5.16), Iraq (HR = 1.34, 95% CI: 1.04-1.74) and Poland (HR = 1.21, 95% CI: 1.02-1.44) and rate of CABG was higher among immigrants from some parts of Asia, including men born in Sri Lanka (HR = 3.19, 95% CI: 1.43-7.12), India (HR = 1.95, 95% CI: 1.21-3.14), Vietnam (HR = 2.65, 95% CI: 1.32-5.33), Palestine State (HR = 2.11, 95% CI: 1.06-4.24), and women born in Syria (HR = 2.36, 95% CI: 1.25-4.45), Iraq (HR = 1.74, 95% CI: 1.02-2.94), and Turkey (HR = 1.70, 95% CI: 1.03-2.79). Conclusions: The observed high rate of CABG for immigrants and particularly those born in some Asian countries was not explained by the potential confounding factors. A more severe coronary disease in this population might explain this high rate but needs further research. Awareness and subsequent intervention at earlier stage of coronary disease among immigrants could prolong their life and reduce the healthcare costs. [ABSTRACT FROM AUTHOR]

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59–0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is a cardiovascular disease with high morbidity and mortality, and microRNA-139-5p (miR-139-5p) has been reported to be closely related with myocardial viability. This study aimed to investigate the effects of miR-139-5p on vascular endothelial cells, detect miR-139-5p expression in AMI patients and evaluate its diagnostic value. A dual-luciferase reporter assay was utilized to confirm the interaction of miR-139-5p with vascular endothelial growth factor receptor-1 (VEGFR-1). Quantitative real-time PCR was used to detect the levels of miR-139-5p and VEGFR-1 in serum and cells. The viability of human umbilical vein endothelial cells (HUVECs) was measured using a cell counting kit-8 assay. The correlation between miR-139-5p and VEGFR-1 was analyzed by Pearson correlation analysis. The diagnostic value of miR-139-5p, cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) was identified by receiver operating characteristic analysis. miR-139-5p suppressed cell viability by directly targeting VEGFR-1 in HUVECs. Increased miR-139-5p and decreased VEGFR-1 levels were found in AMI patients and hypoxia-treated HUVECs, and miR-139-5p and VEGFR-1 were shown to be negatively correlated. The diagnostic value of miR-139-5p for AMI screening was high, and the combination of cTnI, CK-MB and miR-139-5p had the highest diagnostic accuracy. miR-139-5p inhibited cell viability by inhibiting VEGFR-1 in hypoxia-treated HUVECs. miR-139-5p inhibits endothelial cell viability of AMI by inhibiting VEGFR-1, and increased miR-139-5p expression in AMI patients has high diagnostic value for AMI screening, indicating that miR-139-5p may serve as a diagnostic biomarker and molecular therapeutic target for AMI. • miR-139-5p suppressed HUVEC viability by directly inhibiting VEGFR-1. • miR-139-5p was upregulated and VEGFR-1 was downregulated in AMI patients. • Serum miR-139-5p was negatively correlated with serum VEGFR-1. • Increased miR-139-5p had relatively high diagnostic accuracy in AMI. • High miR-139-5p suppressed hypoxia-treated HUVEC viability by inhibiting VEGFR-1. [ABSTRACT FROM AUTHOR]

We investigated if elevated cardiac troponin I (cTnI) serum levels before non-cardiac surgery were predictors of postoperative cardiac events in patients with end stage renal disease (ESRD) undergoing dialysis. In total, 703 consecutive patients with ESRD undergoing dialysis who underwent non-cardiac surgery were enrolled. Preoperative cTnI serum levels were measured at least once in all patients. The primary endpoint was defined as a composite of cardiac death, myocardial infarction (MI), and pulmonary edema during hospitalization or within 30 days after surgery in patients with a hospitalization longer than 30 days after surgery. Postoperative cardiac events occurred in 48 (6.8%) out of 703 patients (cardiac death 1, MI 18, and pulmonary edema 33). Diabetes mellitus (DM), previous ischemic heart disease, and congestive heart failure were more common in patients with postoperative cardiac events. Peak cTnI serum levels were higher in patients with postoperative cardiac event (180 ± 420 ng/L vs. 80 ± 190 ng/L, p = 0.008), and also elevated peak cTnI levels > 45 ng/L were more common in patients with postoperative cardiac events (66.8% vs. 30.5%, p < 0.001). Multivariate logistic regression analysis showed that DM (odds ratio [OR] 2.509, 95% confidence interval [CI] 1.178–5.345, p = 0.017) and serum peak cTnI levels ≥ 45 ng/L (OR 3.167, 95% CI 1.557–6.444, p = 0.001) were independent predictors for the primary outcome of cardiac death/MI/pulmonary edema. Moreover, cTnI levels ≥ 45 ng/L had an incremental prognostic value to the revised cardiac risk index (RCRI) (Chi-square = 23, p < 0.001), and to the combined RCRI and left ventricular ejection fraction (Chi-square = 12, p = 0.001). Elevated preoperative cTnI levels are predictors of postoperative cardiac events including cardiac death, MI, and pulmonary edema in patients with ESRD undergoing non-cardiac surgery. [ABSTRACT FROM AUTHOR]

We developed and assessed whether a novel neutrophil-to-hemoglobin and lymphocyte (NHL) score would improve the ability to predict clinical outcome compared with neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) in acute myocardial infarction (AMI). We examined 13,072 AMI patients from the Korean AMI Registry–National Institute of Health database. NHL score was calculated as follows: NHL score (U) = N/(Hb × L), where N, Hb, and L are baseline blood neutrophil, hemoglobin, and lymphocyte count. The primary outcome was the occurrence of major adverse cerebrocardiovascular events (MACCEs) at 2 years. The NLR, SII, and NHL score were independent predictors of 2-year MACCEs. The area under the curve of the NHL score (0.637) for predicting 2-year MACCEs was significantly higher compared with those of SII (0.589) and NLR (0.607). The NHL score significantly improved the reclassification and integrated discrimination compared with NLR (p < 0.0001) and SII (p < 0.0001). A high NHL score (≥ 0.35 U) was an independent predictor of 2-year MACCEs (adjusted hazard ratio, 1.41; 95% confidence interval, 1.29–1.55; p < 0.001). The NHL score could be a novel model for predicting long-term MACCEs in patients with AMI. [ABSTRACT FROM AUTHOR]

This study sought to determine hospital variation in the use of follow-up stress testing (FUST) and invasive coronary angiography (FUCAG) after percutaneous coronary intervention (PCI). The claims records of 150,580 Korean patients who received PCI in 128 hospitals between 2008 and 2015 were analyzed. Patient were considered to have undergone FUST and FUCAG, when these testings were performed within two years after discharge from the index hospitalization. Hierarchical generalized linear and frailty models were used to evaluate binary and time-to-event outcomes. Hospital-level risk-standardized FUCAG and FUST rates were highly variable across the hospitals (median, 0.41; interquartile range [IQR], 0.27–0.59; median, 0.22; IQR, 0.08–0.39, respectively). The performances of various models predicting the likelihood of FUCAG and FUST were compared, and the best performance was observed with the models adjusted for patient case mix and individual hospital effects as random effects (receiver operating characteristic curves, 0.72 for FUCAG; 0.82 for FUST). The intraclass correlation coefficients of the models (0.41 and 0.68, respectively) indicated that a considerable proportion of the observed variation was related to individual institutional effects. Higher hospital-level FUCAG and FUST rates were not preventive of death or myocardial infarction. Increased repeat revascularizations were observed in hospitals with higher FUCAG rates. [ABSTRACT FROM AUTHOR]

We developed and assessed whether a novel neutrophil-to-hemoglobin and lymphocyte (NHL) score would improve the ability to predict clinical outcome compared with neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) in acute myocardial infarction (AMI). We examined 13,072 AMI patients from the Korean AMI Registry–National Institute of Health database. NHL score was calculated as follows: NHL score (U) = N/(Hb × L), where N, Hb, and L are baseline blood neutrophil, hemoglobin, and lymphocyte count. The primary outcome was the occurrence of major adverse cerebrocardiovascular events (MACCEs) at 2 years. The NLR, SII, and NHL score were independent predictors of 2-year MACCEs. The area under the curve of the NHL score (0.637) for predicting 2-year MACCEs was significantly higher compared with those of SII (0.589) and NLR (0.607). The NHL score significantly improved the reclassification and integrated discrimination compared with NLR (p < 0.0001) and SII (p < 0.0001). A high NHL score (≥ 0.35 U) was an independent predictor of 2-year MACCEs (adjusted hazard ratio, 1.41; 95% confidence interval, 1.29–1.55; p < 0.001). The NHL score could be a novel model for predicting long-term MACCEs in patients with AMI. [ABSTRACT FROM AUTHOR]

Hyponatremia in the early phase of acute myocardial infarction (AMI) is a well-known predictor of poor prognosis. However, little is known about the clinical implication of sodium levels at discharge in hospital survivors after AMI. The study included 1290 consecutive patients (64 ± 12 years; 877 men) who survived the index hospitalization after AMI. We determined the 12-month mortality rates of these patients. Patients who died during the 12-month follow-up had lower sodium levels at discharge than those who had survived (137 ± 6 vs. 139 ± 4 mmol/L; P < 0.014). Hyponatremia at discharge, defined as a serum sodium level ≤135 mmol/L, was present in 210 patients (16.3 %). In the Cox-proportional hazard model, hyponatremia at discharge (hazard ratio, 2.264; 95 % confidence interval, 1.119-4.579; P = 0.023) was an independent predictor of 12-month mortality. Moreover, hyponatremia at discharge had an incremental prognostic value over conventional risk factors ( χ = 7, P = 0.007), and conventional risk factors and log N-terminal Pro-B-type natriuretic peptide combined ( χ = 5, P = 0.021). In the subgroup analysis, the 12-month mortality of patients with hyponatremia at discharge was significantly higher than in those without, irrespective of age, Killip class, left ventricular ejection fraction, percutaneous coronary intervention at index hospitalization, and prescription of diuretics at discharge. Hyponatremia at discharge is an independent predictor of 12-month mortality in hospital survivors after AMI. [ABSTRACT FROM AUTHOR]

No reflow after reperfusion therapy for myocardial infarction is a strong predictor of clinical outcome. Increased levels of inflammatory factors, including C-reactive protein (CRP), in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) may affect myocardial perfusion. However, why the no-reflow phenomenon increases in inflammation stress after PCI is not clear. The aim of the present study was to determine the effects and molecular mechanisms underlying the effects of CRP on the expression of cyclo-oxygenase (COX) on the development of the no-reflow phenomenon. There was a significant increase in plasma levels of CRP and interleukin (IL)-6 in no-reflow patients, suggesting that inflammatory factors play an important role in the development of the no-reflow phenomenon. The mechanisms involved were further evaluated after reperfusion in a rat model mimicking the no-reflow phenomenon. Compared with normal reflow rats, there were significant increases in both COX-1 and COX-2 in cardiac tissue from no-reflow rats. The COX inhibitor indomethacin (5 mg/kg, i.p.) significantly reduced the no-reflow area. In another series of experiments, human coronary artery endothelial cells (HCAEC) were treated with CRP at clinically relevant concentrations (5-25 μg/mL). C-Reactive protein significantly increased COX-1 and COX-2 levels in a time- and concentration-dependent manner. In addition, extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) were activated in CRP (5, 10, 25 μg/mL)-treated HCAEC cultures. Furthermore, the ERK inhibitor pd98059 (30 μmol/L) and the JNK inhibitor sp600125 (10 μmol/L) blocked CRP-induced COX-1 and COX-2 expression for 12 h. Together, the findings of the present study suggest that CRP can promote the development of the no-reflow phenomenon by increasing COX-1 and COX-2 expression, which is regulated, in part, via ERK and JNK activity. [ABSTRACT FROM AUTHOR]