A novel radiomics-based technique for identifying vulnerable coronary plaques: a follow-up study.

BACKGROUND: Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. METHODS: This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. RESULTS: A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. CONCLUSION: Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.

Different prognostic association of systolic blood pressure at different time points with postdischarge events in patients hospitalized for decompensated heart failure.

BACKGROUND: The association of systolic blood pressure (SBP) with mortality in heart failure (HF) patients is paradoxical, and the time points of baseline SBP are also different across prior studies. We hypothesized that the levels of SBP at admission and at discharge had different associations with postdischarge events. METHODS: The study population included patients hospitalized for decompensated HF in the Heart Failure Center of Fuwai Hospital from January 1, 2009 to December 31, 2014. The primary outcome was a composite of cardiovascular (CV) death and heart transplantation. Multivariate Cox proportional-hazards and restricted cubic spline analyses were used to assess the relationships between SBP at different time points and outcomes. RESULTS: In total, 2005 patients were included with a median follow-up of 48.4 months. The median age was 59 years, and 69.9% were male. Multivariate Cox analyses showed that compared with SBP < 105 mmHg, higher SBP at admission was associated with better long-term primary outcome (105-119 mmHg, HR = 0.764, P = 0.005; 120-134 mmHg, HR = 0.658, P < 0.001; ≥ 135 mmHg, HR = 0.657, P = 0.001). Patients whose discharge SBP was higher than 135 mmHg had a similar primary outcome as those with SBP < 105 mmHg (HR = 0.969, P = 0.867), and the results remained unchanged even after adjusting for admission SBP (HR = 1.235, P = 0.291). The results of restricted cubic spline analysis indicated similar associations. CONCLUSIONS: Lower but not higher SBP at admission is associated with more CV deaths/heart transplantations (a reverse J-shaped curve). In contrast, there is a U-shaped association between discharge SBP and CV mortality/heart transplantation.

The circular RNA ACR attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/ FAM65B pathway.

Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.

LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription.

Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H2O2 and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases.

miR-23a Regulates Cardiomyocyte Apoptosis by Targeting Manganese Superoxide Dismutase.

Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

Distribution and clinical association of plasma soluble ST2 during the development of type 2 diabetes.

AIM: ST2 plays important roles in diabetes and cardiovascular diseases. However, the distribution and changes in plasma soluble ST2 during the development of type 2 diabetes remain unclear. METHODS: In the present study, 525 subjects were recruited and divided into three groups: normal, prediabetic and diabetic subjects. The sST2 levels of all subjects were measured using a high-sensitivity assay. RESULTS: sST2 levels were modestly but significantly elevated in patients with diabetes (26.1ng/ml) compared with normal subjects (19.3ng/ml, P<0.001) and persons with prediabetes (20.3ng/ml, P<0.001). The third and fourth quartiles (21.3 and 29.1ng/ml, respectively) of the sST2 levels were associated with a 2.31- and 4.00-fold increased risk of having diabetes. With the prediabetic group as a reference population, patients with sST2 levels in the fourth quartiles had a higher increased risk of having diabetes mellitus (odds ratios=2.19, P<0.05). Furthermore, each SD log sST2 was associated with a 1.57-fold increased risk of atherosclerosis when all relevant variables was added to the multivariable logistic regression models. After adjustment for age and sex, all markers of liver and renal function, HDL-cholesterol, total cholesterol and smoking status showed a significant association with sST2 levels. CONCLUSION: Elevated sST2 levels were not only associated with metabolic characteristics of diabetes but also with a significantly increased risk of having diabetes.

Frequency and predictors of normalization of left ventricular ejection fraction in recent-onset nonischemic cardiomyopathy.

Emerging evidence has shown the potential of marked improvement in left ventricular ejection fraction (LVEF) in patients with recent-onset cardiomyopathy (ROCM) on medical therapy. This study was designed to determine the frequency and to identify predictors of normalization of LVEF in a cohort of Chinese patients with ROCM receiving contemporary medication. A consecutive series of patients admitted from October 2008 to November 2012 with the clinical diagnosis of ROCM and LVEF ≤ 40% by echocardiography at presentation were followed up at least 12 months to identify those with normalization of LVEF, defined as an increase in LVEF to a final level of ≥ 50%. An array of clinical and echocardiographic variables regarded as potentially relevant to normalization was evaluated to identify predictors using logistic regression analysis. After a mean follow-up of 31 ± 13 months, 48% of 128 patients had normalized their LVEF, showing a significant increase in LVEF from 32 ± 6% to 58 ± 5%, of which 68% occurred within 1 year after initial diagnosis. Multivariate analysis demonstrated that normalization of LVEF was associated with a history of hypertension, higher systolic blood pressure at presentation, shorter electrocardiographic QRS duration, smaller left ventricular end-diastolic diameter, and higher LVEF by echocardiography at baseline. In conclusion, nearly 1/2 of a relatively large number of Chinese patients with ROCM have shown normalization of LVEF on current medical therapy after a medium-term follow-up, which was associated with some clinical and echocardiographic parameters.

Very high fructose intake increases serum LDL-cholesterol and total cholesterol: a meta-analysis of controlled feeding trials.

Fructose is widely used as a sweetener in the production of many foods, yet the relation between fructose intake and cholesterol remains uncertain. In this study, we performed a systematic review and meta-analysis of human, controlled, feeding trials involving isocaloric fructose exchange for other carbohydrates to quantify the effects of fructose on serum total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in adult humans. Weighted mean differences were calculated to determine changes from baseline cholesterol concentrations by means of generic, inverse variance, random-effect models. The Heyland Methodological Quality was used to assess the quality of the study. Subgroup analyses and meta-regression were conducted to explore the possible influences of study characteristics. Twenty-four trials (with a total of 474 participants) were included in the meta-analysis. In an overall pooled estimate, it was shown that fructose exerted no effect on HDL-C. Meta-regression analysis indicated that fructose dose was positively correlated with the effect sizes of TC and LDL-C. Subgroup analyses showed that isocaloric fructose exchange for carbohydrates increased TC by 13.0 mg/dL [(95% CI: 4.7, 21.3); P = 0.002] and LDL-C by 11.6 mg/dL [(95% CI: 4.4, 18.9); P = 0.002] at >100 g fructose/d. However, no effect was shown on TC or LDL-C when the fructose intake was ≤100 g/d. In conclusion, it was shown that very high fructose intake (>100 g/d) increases serum LDL-C and TC concentrations. Larger, longer, and higher-quality human, controlled, feeding trials are needed to confirm these results.

Neuregulin-1 attenuates doxorubicin-induced autophagy in neonatal rat cardiomyocytes.

Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in animal models of doxorubicin (DOX)-induced cardiomyopathy, but the underlying mechanism remains largely unknown. Here, we confirm a role for rhNRG-1 in attenuating DOX-induced autophagy and define the signaling pathways through which it mediates some of its effects. Neonatal rat ventricular myocytes were subjected to different treatments both to induce autophagy and to determine the effects of rhNRG-1 on the process. The rhNRG-1 inhibited DOX-induced autophagy, reduced reactive oxygen species production and increased protein expression of Bcl-2, effects that were recapitulated when the cells were treated with the antioxidant N-acetylcysteine. These effects were blocked by the phosphatidylinositol 3-kinase inhibitor LY294002, pointing to the involvement of the Akt pathway in mediating the process. Inhibition of Bcl-2 expression with small interfering RNA silencing also inhibited rhNRG-1's ability to attenuate DOX-induced autophagy. The rhNRG-1 is a potent inhibitor of DOX-induced autophagy and multiple signaling pathways, including Akt and activation of reactive oxygen species, play important roles in the anti-autophagy effect. The rhNRG-1 is a novel drug that may be effectively therapeutically in protecting further damage in DOX-induced damaged myocardium.