MiR-411-5p Promotes Vascular Smooth Muscle Cell Phenotype Switch by Inhibiting Expression of Calmodulin Regulated Spectrin-Associated Protein-1.

When stimulated, vascular smooth muscle cells (VSMCs) change from a differentiated to a dedifferentiated phenotype. Dedifferentiated VSMCs have a key activity in cardiovascular diseases such as in-stent restenosis. MicroRNAs (miRNAs) have crucial functions in conversion of differentiated VSMCs to a dedifferentiated phenotype. We investigated the activity of miR-411-5p in the proliferation, migration, and phenotype switch of rat VSMCs.Based on a microRNA array assay, miR-411-5p expression was found to be significantly increased in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB). A CCK-8 assay, transwell assay, and scratch test were performed to measure the effect of miR-411-5p on the proliferation and migration of PDGF-BB-treated VSMCs. MiR-411-5p promoted expression of dedifferentiated phenotype markers such as osteopontin and tropomyosin 4 in PDGF-BB-treated VSMCs. Using mimics and inhibitors, we identified the target of miR-411-5p in PDGF-BB-treated VSMCs and found that calmodulin-regulated spectrin-associated protein-1 (CAMSAP1) was involved in the phenotypic switch mediated by PDGF-BB.By inhibiting expression of CAMSAP1, miR-411-5p enhanced the proliferation, migration, and phenotype switch of VSMCs.Blockade of miR-411-5p interaction with CAMSAP1 is a promising approach to treat in-stent restenosis.

The relationship between perioperative serum albumin and contrast-induced acute kidney injury in patients after percutaneous coronary intervention.

OBJECTIVE: Contrast-induced acute kidney injury (CI-AKI) is a common complication in patients undergoing percutaneous coronary intervention (PCI). Studies have shown that perioperative serum albumin levels may play a role in the occurrence of CI-AKI. In this study, we aimed to investigate the effect of perioperative serum albumin (delta albumin or &Alb) levels on the occurrence and long-term prognosis of CI-AKI patients after PCI. METHODS: A total of 959 patients who underwent PCI between January 2017 and January 2019 were selected for this study. A receiver operating characteristic curve was used to determine the optimal cut-off value of the &Alb level for predicting CI-AKI after PCI. Patients were divided into two groups based on the optimal cut-off value: the high &Alb group (&Alb ≥ 4.55 g/L) and the control group (&Alb < 4.55 g/L). The incidences of CI-AKI and major adverse cardiac events (MACEs, including all-cause death, nonfatal myocardial infarction, and target vessel revascularization) were compared between the groups. Cox regression analysis was used to identify predictors of long-term prognosis after PCI. RESULTS: Of the 959 patients, 147 (15.3%) developed CI-AKI after PCI. The CI-AKI group had a greater level of &Alb than did the non-CI-AKI group [(6.14 (3.90-9.10) versus 3.48 (4.31-6.57), P < 0.01)]. The incidence of CI-AKI in the high &Alb group was significantly greater than that in the low group (23.6% versus 8.3%, P < 0.01). After a 1-year follow-up, the incidence of MACEs was significantly greater in the high &Alb group than in the low group (18.6% versus 14.5%, P = 0.030). Cox regression analysis confirmed that CI-AKI was an independent predictor of MACEs at the 1-year follow-up (HR 1.43, 95% CI 1.04-1.96, P = 0.028). In addition, patients with low preoperative serum albumin levels had s significantly greater incidence of MACEs than did those with high preoperative serum albumin levels (23.2% versus 19.5%, P = 0.013). CONCLUSION: In summary, high baseline &Alb levels are an independent risk factor for CI-AKI in patients after PCI. The occurrence of CI-AKI in the perioperative period is also an independent predictor of long-term prognosis after PCI. These findings highlight the importance of monitoring &Alb levels and taking steps to prevent CI-AKI in patients undergoing PCI.

Relationship between indices of insulin resistance and incident type 2 diabetes mellitus in Chinese adults.

BACKGROUND: Insulin resistance (IR) is a pivotal pathogenesis characteristic of type 2 diabetes mellitus (T2DM). The current study aimed to explore the association between triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), triglyceride-glucose (TyG), and triglyceride glucose-body mass index (TyG-BMI), and T2DM incidence. METHODS: A total of 116,855 Chinese adults aged over 20 without diabetes were included. Multivariate Cox regression analysis and restricted cubic spine were utilized to investigate the association between IR indicators and T2DM. The T2DM risk across different quartiles of IR parameters was compared using Kaplan-Meier curves. The receiver operating characteristic analysis was used to investigate the predictive potential of each IR indicator for future T2DM. RESULTS: A total of 2685 participants developed T2DM during a median follow-up of 2.98 years. The adjusted hazard ratios (HR) of incident T2DM were 1.177, 2.766, and 1.1018 for TG/HDL-c, TyG, and TyG-BMI, respectively. There were significant increasing trends of T2DM across the quartiles of TG/HDL-c, TyG, and TyG-BMI. The HRs of new-onset T2DM in the highest quartiles versus the lowest quartile of TG/HDL-c, TyG, and TyG-BMI were 3.298, 8.402, and 8.468. RCS revealed the nonlinear relationship between IR and T2DM risk. The correlations between IR and T2DM were more pronounced in subjects aged <40. TyG-BMI had the highest predictive value for incident T2DM (AUC = 0.774), with a cut-off value of 213.289. CONCLUSION: TG/HDL-c, TyG, and TyG-BMI index were all significantly positively associated with higher risk for future T2DM. Baseline TyG-BMI level had high predictive value for the identification of T2DM.

Identifying metabolic dysfunction-associated steatotic liver disease in patients with hypertension and pre-hypertension: An interpretable machine learning approach.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent liver diseases and is associated with pre-hypertension and hypertension. Our research aims to develop interpretable machine learning (ML) models to accurately identify MASLD in hypertensive and pre-hypertensive populations. Methods: The dataset for 4722 hypertensive and pre-hypertensive patients is from subjects in the NAGALA study. Six ML models, including the decision tree, K-nearest neighbor, gradient boosting, naive Bayes, support vector machine, and random forest (RF) models, were used in this study. The optimal model was constructed according to the performances of models evaluated by K-fold cross-validation (k = 5), the area under the receiver operating characteristic curve (AUC), average precision (AP), accuracy, sensitivity, specificity, and F1. Shapley additive explanation (SHAP) values were employed for both global and local interpretation of the model results. Results: The prevalence of MASLD in hypertensive and pre-hypertensive patients was 44.3% (362 cases) and 28.3% (1107 cases), respectively. The RF model outperformed the other five models with an AUC of 0.889, AP of 0.800, accuracy of 0.819, sensitivity of 0.816, specificity of 0.821, and F1 of 0.729. According to the SHAP analysis, the top five important features were alanine aminotransferase, body mass index, waist circumference, high-density lipoprotein cholesterol, and total cholesterol. Further analysis of the feature selection in the RF model revealed that incorporating all features leads to optimal model performance. Conclusions: ML algorithms, especially RF algorithm, improve the accuracy of MASLD identification, and the global and local interpretation of the RF model results enables us to intuitively understand how various features affect the chances of MASLD in patients with hypertension and pre-hypertension.

Nonlinear relationship between untraditional lipid parameters and the risk of prediabetes: a large retrospective study based on Chinese adults.

BACKGROUND: Abnormal lipid metabolism poses a risk for prediabetes. However, research on lipid parameters used to predict the risk of prediabetes is scarce, and the significance of traditional and untraditional lipid parameters remains unexplored in prediabetes. This study aimed to comprehensively evaluate the association between 12 lipid parameters and prediabetes and their diagnostic value. METHODS: This cross-sectional study included data from 100,309 Chinese adults with normal baseline blood glucose levels. New onset of prediabetes was the outcome of concern. Untraditional lipid parameters were derived from traditional lipid parameters. Multivariate logistic regression and smooth curve fitting were used to examine the nonlinear relationship between lipid parameters and prediabetes. A two-piecewise linear regression model was used to identify the critical points of lipid parameters influencing the risk of prediabetes. The areas under the receiver operating characteristic curve estimated the predictive value of the lipid parameters. RESULTS: A total of 12,352 participants (12.31%) were newly diagnosed with prediabetes. Following adjustments for confounding covariables, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were negatively correlated with prediabetes risk. Conversely, total cholesterol, triglyceride (TG), lipoprotein combine index (LCI), atherogenic index of plasma (AIP), non-HDL-C, atherogenic coefficient, Castelli's index-I, remnant cholesterol (RC), and RC/HDL-C ratio displayed positive correlations. In younger adults, females, individuals with a family history of diabetes, and non-obese individuals, LCI, TG, and AIP exhibited higher predictive values for the onset of prediabetes compared to other lipid profiles. CONCLUSION: Nonlinear associations were observed between untraditional lipid parameters and the risk of prediabetes. The predictive value of untraditional lipid parameters for prediabetes surpassed that of traditional lipid parameters, with LCI emerging as the most effective predictor for prediabetes.

Identification of hub genes based on integrated analysis of single-cell and microarray transcriptome in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating chronic cardiopulmonary disease without an effective therapeutic approach. The underlying molecular mechanism of PAH remains largely unexplored at single-cell resolution. METHODS: Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database (GSE210248) was included and analyzed comprehensively. Additionally, microarray transcriptome data including 15 lung tissue from PAH patients and 11 normal samples (GSE113439) was also obtained. Seurat R package was applied to process scRNA-seq data. Uniform manifold approximation and projection (UMAP) was utilized for dimensionality reduction and cluster identification, and the SingleR package was performed for cell annotation. FindAllMarkers analysis and ClusterProfiler package were applied to identify differentially expressed genes (DEGs) for each cluster in GSE210248 and GSE113439, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) were used for functional enrichment analysis of DEGs. Microenvironment Cell Populations counter (MCP counter) was applied to evaluate the immune cell infiltration. STRING was used to construct a protein-protein interaction (PPI) network of DEGs, followed by hub genes selection through Cytoscape software and Veen Diagram. RESULTS: Nineteen thousand five hundred seventy-six cells from 3 donors and 21,896 cells from 3 PAH patients remained for subsequent analysis after filtration. A total of 42 cell clusters were identified through UMAP and annotated by the SingleR package. 10 cell clusters with the top 10 cell amounts were selected for consequent analysis. Compared with the control group, the proportion of adipocytes and fibroblasts was significantly reduced, while CD8+ T cells and macrophages were notably increased in the PAH group. MCP counter revealed decreased distribution of CD8+ T cells, cytotoxic lymphocytes, and NK cells, as well as increased infiltration of monocytic lineage in PAH lung samples. Among 997 DEGs in GSE113439, module 1 with 68 critical genes was screened out through the MCODE plug-in in Cytoscape software. The top 20 DEGs in each cluster of GSE210248 were filtered out by the Cytohubba plug-in using the MCC method. Eventually, WDR43 and GNL2 were found significantly increased in PAH and identified as the hub genes after overlapping these DEGs from GSE210248 and GSE113439. CONCLUSION: WDR43 and GNL2 might provide novel insight into revealing the new molecular mechanisms and potential therapeutic targets for PAH.

The Differences of Quantitative Flow Ratio in Coronary Artery Stenosis with or without Atrial Fibrillation.

Quantitative flow ratio (QFR) is a new method for the assessment of the extent of coronary artery stenosis. But it may be obscured by the cardiac remodeling and abnormal blood flow of the coronary artery when encountering atrial fibrillation (AF). The present study aimed to examine the impact of these changed structures and blood flow of coronary arteries on QFR results in AF patients. Methods and Results. We evaluated QFR in 223 patients (112 patients with AF; 111 non-AF patients served as controls) who had undergone percutaneous coronary intervention (PCI) due to severe stenoses in coronary arteries. QFR of the target coronary was determined according to the flow rate of the contrast agent. Results showed that AF patients had significantly higher QFR values than control (0.792 ± 0.118 vs. 0.685 ± 0.167, p < 0.001). We further analyzed local QFR around the stenoses (0.858 ± 0.304 vs. 0.756 ± 0.146, p=0.002), residual QFR (0.958 ± 0.055 vs. 0.929 ± 0.093, p=0.005), and index QFR (0.807 ± 0.108 vs. 0.713 ± 0.152, p < 0.001) in these two groups of patients with and without AF. Further analysis revealed that QFR in AF patients was negatively correlated with coronary flow velocity (R = -0.22, p=0.02) and area of stenosis (R = -0.70, p < 0.001) but positively correlated with the minimum lumen area (MLA) (R = 0.47, p < 0.001). Conclusion. AF patients with coronary artery stenosis have higher QFR values, which are associated with decreased blood flow velocity, smaller stenosis, and larger MLA in AF patients upon cardiac remodeling.

Upregulation of the key biomarker kinesin family member 20A (KIF20A) is associated with pulmonary artery hypertension.

OBJECTIVE: Pulmonary artery hypertension (PAH) is a complex, fatal disease with limited treatments. This study aimed to investigate possible key targets in PAH through bioinformatics. METHODS: GSE144274 were obtained from Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) between idiopathic pulmonary hypertension (IPAH) and healthy subjects were identified and analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed, and a protein-protein interaction (PPI) network was constructed using STRING. The hub genes were identified by MCODE method. The expression levels of hub genes were validated in vitro and in vivo models. Finally, the ROC analysis was performed based on the level of hub genes in clinical plasma samples. RESULTS: A total of 363 DEGs were identified. GO analysis on these DEGs were mainly enriched in cell division, inflammatory response, among others. In the KEGG pathways analysis, DEGs mainly involved in cytokine-cytokine receptor interaction, rheumatoid arthritis, and IL-17 signaling pathways were enriched. The DEGs were analyzed with the STRING for PPI network analysis, and 62 hub genes were identified by MCODE. Finally, 6 central genes, KIF18B, SPC25, DLGAP5, KIF20A, CEP55 and ANLN, were screened out due to their novelty role in PAH. The expression of KIF20A was validated to be significantly upregulated both in the lung tissue of hypoxia-induced pulmonary hypertension (HPH) mice and proliferative PASMCs. Additionally, KIF20A levels is evelated in PAH plasma and the area under the curve (AUC) to identify PAH was 0.8591 for KIF20A. CONCLUSION: The level of KIF20A elevates during the progression of PAH, which suggestes it could be a potential diagnostic and therapeutic target for the PAH.

De Ritis Ratio is Associated with Contrast-Associated Acute Kidney Injury Prediction and Long-Term Clinical Outcomes in Patients Undergoing Emergency Percutaneous Coronary Intervention.

Contrast-associated acute kidney injury (CA-AKI) is a familiar complication following percutaneous coronary intervention (PCI). The present study evaluated the predictive value of the De Ritis ratio for CA-AKI and its association with long-term clinical outcomes in patients undergoing emergency PCI. Overall, 546 patients were included in this study. The De Ritis ratio was calculated by aspartate aminotransferase/alanine aminotransferase activity. The De Ritis ratios in the CA-AKI patients were significantly higher than the non-CA-AKI patients [3.74 (2.32, 4.90) vs 1.61 (1.02, 2.53); P < .001]. The De Ritis ratio was an independent risk factor for CA-AKI [odds ratio, 2.243; 95% confidence interval (CI), 1.823-2.759; P < .001]. The area under the ROC curve was .813 (95% CI, .763-.862; P < .001), and the sensitivity and specificity were 67.0% and 82.4%, respectively, when the optimum cut-off value was 2.97. Furthermore, patients in the high De Ritis ratio group (≥1.76) had a significantly greater incidence of primary endpoints [26.7% (73/273) vs 13.2% (36/273); P < .001], and the high De Ritis ratio was an independent predictor for primary endpoints (hazard ratio, 1.888, 95% CI, 1.235-2.887; P = .003). In conclusion, the De Ritis Ratio is associated with CA-AKI prediction and long-term clinical outcomes in patients undergoing emergency PCI.

Association Between Inflammatory Biomarkers and Contrast-induced Acute Kidney Injury in ACS Patients Undergoing Percutaneous Coronary Intervention: A Cross-sectional Study.

The present study aimed to evaluate the predictive role of inflammatory biomarkers in the development of contrast-induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The inflammatory biomarkers assessed were: platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), neutrophil-to-lymphocyte*platelet ratio (NLPR), systemic inflammatory index (SII), and systemic inflammation response index (SIRI). Overall, 950 patients undergoing PCI were enrolled. The frequency of CI-AKI was 15.2% (n = 144). The levels of NLR, MLR, NLPR, SII, and SIRI were higher in the CI-AKI group than in the Non-CI-AKI group (P < .05). The addition of NLR ≥2.96, dNLR ≥2.08, NLPR ≥.012, SII ≥558.04, and SIRI ≥1.13 to the Mehran score model significantly increased the area under the curve (P < .05). Multivariable logistic regression analyses indicated that inflammatory biomarkers were significantly associated with CI-AKI, including NLR ≥2.96 (OR = 1.588, P = .017), dNLR ≥2.08 (OR = 1.686, P = .007), SII ≥558.04 (OR = 1.521, P = .030), and SIRI ≥1.13 (OR = 1.601, P = .017). Therefore, inflammation is associated with the development of CI-AKI, and preoperative hematological inflammatory markers could predict the risk of CI-AKI in ACS patients undergoing PCI.

Predicting cerebral white matter lesions based on the platelet-to-white blood cell ratio in hypertensive patients.

Hypertension is a common chronic disease affecting many people. White matter lesions (WMLs) are one of the imaging features of cerebrovascular disease. Predicting the possibility of developing syncretic WMLs in patients with hypertension may contribute to the early identification of serious clinical conditions. This study aims to build a model to identify patients who suffered from moderate-to-severe WMLs by using recognized WMLs risk factors including age and history of diabetes and a new factor named platelet-to-white blood cell ratio (PWR). A total of 237 patients were included in this study. The Affiliated ZhongDa Hospital of Southeast University Research Ethics Committee approved this study (Ethics No. 2019ZDSYLL189-P01). We developed a nomogram to predict the risk of syncretic WMLs in patients with hypertension using the above factors. Higher total scores on the nomogram indicated a higher risk of syncretic WMLs. This means older age, smaller PWR, and patients suffering from diabetes contributed to a greater chance for the patient to suffer from syncretic WMLs. We used a decision analysis curve(DCA) to determine the net benefit of the prediction model. The DCA we constructed showed that using our model to decide whether patients suffered from syncretic WMLs or not was better than assuming they all suffered from syncretic WMLs or all WMLs-free. As a result, the area under the curve of our model was 0.787. By integrating PWR, history of diabetes, and age, we could estimate integrated WMLs in hypertensive patients. This study provides a potential tool to identify cerebrovascular disease in patients with hypertension.

Visceral adiposity index is positively associated with fasting plasma glucose: a cross-sectional study from National Health and Nutrition Examination Survey 2017-2020.

BACKGROUND: Visceral adiposity index (VAI) has been recognized as a reliable indicator for visceral adiposity. However, it remains largely unexplored on its association with fasting plasma glucose (FPG). The current study aims to explore the association between VAI and FPG using a representative dataset. METHODS: A cross-sectional study was carried out based on the dataset from National Health and Nutrition Examination Survey (NHANES) 2017-2020. Univariate and Multiple linear regression analysis were performed to explore the relationship between VAI and FPG. Generalized additive model (GAM) and smooth curve fitting analysis were performed to explore the nonlinear relationship between VAI and FPG. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive value of VAI for FPG elevation. RESULTS: A total of 4437 participants with complete data were finally included in the research. Individuals were divided into 4 quartiles according to the calculated VAI value: Q1 (VAI<0.69), Q2 (0.69 ≤ VAI < 1.18), Q3 (1.18 ≤ VAI < 2.02) and Q4 (VAI ≥ 2.02). FPG significantly increased with the increasing VAI quartile. Multiple linear regression analysis showed VAI was independently positively associated with FPG after adjusting confounding factors. As a continuous variable, an increase of one unit in VAI was correlated with 0.52 mmol/L (95% CI: 0.41-0.63, p < 0.0001) higher FPG level. As a categorical variable, 4th VAI quartile group was related to 0.71 mmol/L (95% CI: 0.47-0.95, p < 0.001) higher FPG level compared with 1st VAI group. GAM and smooth curve fitting analysis identified the non-linear relationship between VAI and FPG, and 4.02 was identified as the inflection point using two-piecewise linear regression. The positive association between VAI and FPG existed when VAI was lower (ß = 0.73, p < 0.0001) and higher than 4.02 (ß = 0.23, p = 0.0063). ROC analysis indicated VAI has a good predictive value for FPG elevation (AUC = 0.7169, 95% CI: 0.6948-0.7389), and the best threshold of VAI was 1.4315. CONCLUSION: VAI was an independently risk indicator for FPG, and VAI was nonlinearly positively associated with FPG. VAI had a good predictive value for elevated FPG. VAI might become a useful indicator for risk assessment and treatment of hyperglycemia in clinical practice.

Association between uric acid level and contrast-induced acute kidney injury in patients with type 2 diabetes mellitus after coronary angiography: a retrospective cohort study.

BACKGROUND: This study assessed the predictive value of uric acid (UA) for contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) who underwent coronary angiography (CAG). A nomogram to aid in the prediction of CI-AKI was also developed and validated, and the construction of a prognostic nomogram combined with clinical features was attempted. METHODS: This study retrospectively enrolled T2DM patients who underwent CAG between December 2019 and December 2020 at the Affiliated Zhongda Hospital of Southeast University. Multivariable logistic regression analysis was used for the analysis of clinical outcomes. Receiver operating characteristic (ROC) analyses were performed to determine the area under the ROC curve (AUC) and the cut-off points for continuous clinical data. The prediction accuracies of models for CI-AKI were estimated through Harrell's concordance indices (C-index). Nomograms of the prognostic models were plotted for individualized evaluations of CI-AKI in T2DM patients after CAG. RESULTS: A total of 542 patients with T2DM who underwent CAG were included in this study. We found that a high UA level (≥ 425.5 µmol/L; OR = 6.303), BUN level (≥ 5.98 mmol/L; OR = 3.633), Scr level (≥ 88.5 µmol/L; OR = 2.926) and HbA1C level (≥ 7.05%; OR = 5.509) were independent factors for CI-AKI in T2DM patients after CAG. The nomogram model based on UA, BUN, Scr and HbA1C levels presented outstanding performance for CI-AKI prediction (C-index: 0.878). Decision curve analysis (DCA) showed good clinical applicability in predicting the incidence of CI-AKI in T2DM patients who underwent CAG. CONCLUSION: High UA levels are associated with an increased incidence of CI-AKI in T2DM patients after CAG. The developed nomogram model has potential predictive value for CI-AKI and might serve as an economic and efficient prognostic tool in clinical practice.

The Association of Serum AIM2 Level with the Prediction and Short-Term Prognosis of Coronary Artery Disease.

Objective: Coronary artery disease (CAD), one of the commonest cardiovascular diseases, has high morbidity and mortality. Absent in melanoma 2 (AIM2) is involved in atherosclerosis, and no clinical trials have explored the association between AIM2 and CAD. Therefore, this study was aimed at evaluating the predictive and short-term prognostic value of AIM2 for CAD. Methods: 279 patients who underwent coronary angiography were enrolled in this study. The AIM2 level was detected from the serum of collected artery blood samples. The association of serum AIM2 level with the prediction and short-term prognosis of CAD was further assessed. Results: The serum AIM2 level of the CAD group was significantly higher than the control group (5.5 ± 2.1 vs. 3.7 ± 1.7; p < 0.001). AIM2 was demonstrated to be the risk factor of CAD [odds ratio, 1.589; 95% confidence interval (CI), 1.346-1.876; p < 0.001]. The area under the receiver operating characteristic (ROC) curve of 0.738 showed the diagnostic value of AIM2 in CAD. Additionally, AIM2 was an independent predictor of major adverse cardiovascular events (hazard ratio, 1.453; 95% CI, 1.086-1.945; p = 0.012), and CAD patients with high AIM2 levels (>4.9 ng/mL) had a markedly lower survival rate (log-rank p = 0.040). Conclusions: The serum AIM2 level > 4.9 ng/mL can predict CAD to a certain extent. AIM2 might be an independent predictor of its short-term poor prognosis.

Microalbuminuria Complicated with Low Estimated Glomerular Filtration Rate: Early Risk Factors for Contrast-Induced Acute Kidney Injury After Coronary Intervention.

BACKGROUND We aimed to investigate the impact of microalbuminuria complicated with low estimate glomerular filtration rate (eGFR) on the incidence and prognosis of contrast-induced acute kidney injury (CI-AKI) in patients with coronary artery disease after coronary intervention. MATERIAL AND METHODS A total of 943 patients were enrolled in the study. Based on microalbumin/creatinine (ACR) measurements, the patients were divided into a microalbuminuria cohort (MA; 222 patients) and a normal albuminuria cohort (NA; 721 patients). According to eGFR levels, the cohorts were further subdivided into normal, mild, moderate, and severe renal dysfunction groups. The basic data and indicators of all enrolled patients were collected. The patients were followed up at 30 days, 6 months, 1 year, and 3 years after surgery. RESULTS The overall incidence of CI-AKI in the MA cohort was higher than that in the NA cohort (17.6% vs 8.2%, P.

Target Nuclear Factor Erythroid 2-Related Factor 2 in Pulmonary Hypertension: Molecular Insight into Application.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor involved in maintaining redox balance and activates the expression of downstream antioxidant enzymes. Nrf2 has received wide attention considering its crucial role in oxidative and electrophilic stress. Large amounts of studies have demonstrated the protective role of Nrf2 activation in various pulmonary hypertension (pH) models. Additionally, various kinds of natural phytochemicals acting as Nrf2 activators prevent the development of pH and provide a novel and promising therapeutic insight for the treatment of pH. In the current review, we give a brief introduction of Nrf2 and focus on the role and mechanism of Nrf2 in the pathophysiology of pH and then review the relevant research of Nrf2 agonists in pH in both experimental research and clinical trials.

Dapagliflozin Attenuates Contrast-induced Acute Kidney Injury by Regulating the HIF-1α/HE4/NF-κB Pathway.

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) causes clinically acquired nephropathy in patients who undergo coronary interventions. Hypoxic injury to proximal tubular epithelial cells is a pathological mechanism of CI-AKI. Previous studies have shown that hypoxia activates HIF-1α/HE4/NF-κB to enhance renal fibrosis, and the SGLT-2 inhibitor luseogliflozin inhibits hypoxia-inducible factor (HIF)-1α expression to reduce the progression of diabetic nephropathy. However, the therapeutic effects and mechanisms of SGLT-2 inhibitors on CI-AKI are unclear. We explored the role of the HIF-1α/HE4/NF-κB pathway in CI-AKI and how dapagliflozin effectively treats CI-AKI by inhibiting this pathway. In vitro, cells were divided into the control, hypoxia, hypoxia + dapagliflozin, and hypoxia + pSilencer-HIF-1α groups. Cellular hypoxia, apoptosis, and related protein expression were evaluated by immunofluorescence, western blotting, and flow cytometry, respectively. Dapagliflozin significantly decreased oxygen consumption, HIF-1α, human epididymis protein 4 (HE4), NF-κB expression, and apoptotic cells compared with the control (P < 0.01). In vivo, rats were divided into the control (C), diabetes (D), diabetes + contrast media, and diabetes + contrast media + dapagliflozin groups. Rats in the latter 2 groups were treated with dapagliflozin for 2 days. CI-AKI was induced by intravenously injecting indomethacin, N-nitro-l-arginine methyl ester, and iohexol. The effects of dapagliflozin on CI-AKI rats were elucidated by assessing renal function, H&E staining, and immunohistochemistry. Serum creatinine, urea nitrogen, TUNEL-positive tubular cells, HIF-1α, HE4, NF-κB expression, and histopathological scores were increased in diabetes + contrast media rats compared with C, D, and diabetes + dapagliflozin + contrast media rats (P < 0.01). Thus, dapagliflozin may ameliorate CI-AKI through suppression of HIF-1α/HE4/NF-κB signaling in vitro and in vivo.

Elevated TyG Index Predicts Incidence of Contrast-Induced Nephropathy: A Retrospective Cohort Study in NSTE-ACS Patients Implanted With DESs.

Background: Triglyceride-glucose (TyG) index is a reliable and specific biomarker for insulin resistance and is associated with renal dysfunction. The present study sought to explore the relationship between TyG index and the incidence of contrast-induced nephropathy (CIN) in non-ST elevation acute coronary syndrome (NSTE-ACS) patients implanted with drug-eluting stents (DESs). Methods: A total of 1108 participants were recruited to the study and assigned to two groups based on occurrence of CIN. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Baseline characteristics and incidence of CIN were compared between the two groups. Logistic regression analysis was performed to evaluate the relationship between TyG index and CIN. Results: The results showed that 167 participants (15.1%) developed CIN. Subjects in the CIN group had a significantly higher TyG index compared with subjects in the non-CIN group (8.9 ± 0.7 vs. 9.3 ± 0.7, P<0.001). TyG index was significantly correlated with increased risk of CIN after adjusting for confounding factors irrespective of diabetes mellitus status and exhibited a J-shaped non-linear association. Subgroup analysis showed a significant gender difference in the relationship between TyG index and CIN. Receiver operating characteristic (ROC) curve analysis indicated that the risk assessment performance of TyG index was superior compared with other single metabolic indexes. Addition of TyG index to the baseline model increased the area under the curve from 0.713 (0.672-0.754) to 0.742 (0.702-0.782) and caused a reclassification improvement of 0.120 (0.092-0.149). Conclusion: The findings from the present study show that a high TyG index is significantly and independently associated with incidence of CIN in NSTE-ACS patients firstly implanted with DESs. Routine preoperative assessment of TyG index can alleviate CIN and TyG index provides a potential target for intervention in prevention of CIN.

Tolvaptan Improves Contrast-Induced Acute Kidney Injury.

OBJECTIVE: Contrast-induced acute kidney injury (CI-AKI) is a serious side effect of contrast media use. The purpose of this study was to investigate the role and mechanism of tolvaptan (TOL) in CI-AKI. METHODS: 24 Wistar male rats were randomly divided into 4 groups (n = 6). And a rat model of CI-AKI was established. Then, the blood and urine of rats in each group were collected to detect relevant parameters. HE staining was utilized for the observation of the pathological changes of rat kidney tissues, TUNEL assay for the detection of tubular cell apoptosis, biochemical detection for the confirmation of oxidative stress level in kidney tissues, and western blot for the test of the expression of apoptotic proteins and the Nrf2 signaling pathway-related proteins in kidney tissues. RESULTS: TOL could significantly reduce the serum level of urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decrease serum Cys-C and urine KIM-1 in CI-AKI rats. The result above meant that TOL could improve kidney injury and reduce tubular cell apoptosis in CI-AKI rats. In addition, TOL contributed to a reduction of oxidative stress level by downregulating myeloperoxidase level and increasing the activities of superoxide dismutase and glutathione peroxidase in the kidney tissue of CI-AKI rats. After the pretreatment of TOL, the expression of proapoptotic proteins cleaved-caspase 3 and BAX, as well as mitochondrial fusion proteins DRP1 and MFN2 was downregulated, while the expression of Bcl-2 and PINK1 was upregulated in the kidney tissue of CI-AKI rats. Further, TOL could activate the Nrf2 signaling pathway, and the Nrf2 inhibitor ML385 reversed the effect of TOL on CI-AKI. CONCLUSION: TOL can improve CI-AKI by activating the Nrf2/HO-1 signaling pathway, inhibiting oxidative stress response, and reducing tubular cell apoptosis.