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.

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.

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.

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.

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.

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.

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.

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.

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.

Protease-activated receptor 2 deficiency in hematopoietic lineage protects against myocardial infarction through attenuated inflammatory response and fibrosis.

Ischaemic heart disease is one of the leading causes of death. Protease-activated receptor 2 (PAR2) is widely expressed within the cardiovascular system and is known to mediate inflammatory processes in various immunocytes, such as macrophages, mastocytes and neutrophils. Here, we investigated whether activating macrophage PAR2 modulates cardiac remodelling in a murine model of myocardial infarction. Myocardial infarction was produced by the permanent ligation of the left anterior descending coronary artery (LAD) in C57BL/6J background wild-type (WT) mice transplanted with bone marrow from WT or PAR2 knockout (PAR2 KO) mice. Hematopoietic deficiency of PAR2 had improvement of left ventricular systolic dysfunction and dilatation and decreased fibrosis deposition in remote zone at 1 week after LAD ligation. Inactivation of PAR2 also led to less recruitment of macrophages in myocardium, which was accompanied by decreased expression of pro-inflammatory cytokines. Furthermore, cultured cardiac fibroblasts (CFs) were activated and showed a fibrotic phenotype after being co-cultured in medium containing PAR2-activating macrophage, which enhances interferon-beta (INF-ß) expression. The beneficial effects of macrophages with INF-ß neutralisation or PAR2-deletion ameliorates the JAK/STAT3 pathway in CFs, which might be attributed to CF activation. These data suggest that macrophage-derived IFN-ß plays a crucial role in adverse cardiac remodelling after myocardial infarction, at least in part, through a PAR2-dependent mechanism.

Predictive value of random blood glucose versus fasting blood glucose on in-hospital adverse events in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: We aim to find out the relationship between random blood glucose (RBG), fasting blood glucose (FBG) and in-hospital adverse events in ST-segment elevation acute myocardial infarction (STEMI) patients. We evaluate and compare the predictive value of RBG and FBG on in-hospital adverse events, and give an appropriate cut-off value of RBG and FBG. METHOD: A retrospective study enrolled 958 consecutive AMI patients undergoing emergency coronary angiography at Zhongda Hospital were enrolled from January 1, 2016, to December 31, 2018 was performed. RBG and FBG, baseline data and adverse events were recorded. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as death, nonfatal recurrent myocardial infarction and stroke. Other adverse events included malignant arrhythmia, cardiac shock and hemorrhage. Patients with RBG > 11.1 mmol/L were divided into elevated RBG group. Patients with FBG > 6.1 mmol/L were divided into elevated FBG group. The incidence of in-hospital adverse events were compared in elevated RBG/FBG group and the control group. ROC curve was used to evaluate the predictive value of RBG and FBG on in-hospital adverse events. RESULT: The incidence of death, hemorrhage, cardiac shock and malignant arrhythmia significantly increases in elevated RBG and FBG group. Binary logistic regression showed that age, hypertension, diabetes, FBG and RBG were independent risk factors for in-hospital adverse events in STEMI patients. The AUC and 95% CI of RBG and FBG in predicting death of AMI patients were 0.789, 0.759~0.816; 0.810, 0.783~0.835, respectively. The cut-off values ​were 13.82 and 7.35 mmol/L. RBG and FBG also had fine predictive value on cardiac shock and malignant arrhythmia, no statistical difference was found in the predictive value on in-hospital adverse events (P = 0.462, P = 0.570, P = 0.694). CONCLUSION: Incidence of in-hospital adverse events significantly increases in AMI patients combined with elevated RBG or FBG. Both RBG and FBG were independent risk factors for in-hospital adverse events, they had good value on predicting in-hospital adverse events and there was no statistical difference in their predictive value.

Role of integrin-linked kinase in the hypoxia-induced phenotypic transition of pulmonary artery smooth muscle cells: Implications for hypoxic pulmonary hypertension.

The phenotypic transition of pulmonary artery smooth muscle cells (PASMCs) from a contractile/differentiated to synthetic/de-differentiated phenotype is an important mechanism for the occurrence and development of hypoxic pulmonary hypertension (HPH). Integrin-linked kinase (ILK) is an early hypoxic response factor whose kinase activity is significantly affected during early hypoxia. Myocardin and ETS-like protein 1 (Elk-1) are co-activators of serum response factor (SRF) and can bind to SRF to mediate the phenotypic transition of PASMCs. However, little is known about the role of ILK on the phenotypic transition of these PASMCs. Thus, in our study, we explored the role of ILK in this process. We found that the expression of ILK and myocardin decreased gradually with the increase in hypoxia exposure time in the pulmonary arteries of rats. We observed that hypoxia exposure for 1 h caused an increase in the phosphorylation of Elk-1 but did not affect the expression of ILK, myocardin, or SRF. Exposure to hypoxic treatment for 1 h decreased ILK kinase activity and caused Elk-1 to suppress myocardin binding to SRF and the smooth muscle (SM) α-actin gene promoters. In addition, hypoxia exposure for 24 h decreased the expression of ILK, myocardin, SM α-actin, and calponin but increased the expression of osteopontin. Silencing of the myocardin gene significantly decreased the expression of SM α-actin and calponin but increased the expression of osteopontin. Silencing of the ILK gene significantly decreased the expression of myocardin, SM α-actin, and calponin but increased the expression of osteopontin. ILK overexpression reversed the effects of 24 h of hypoxia on the expression of myocardin, SM α-actin, calponin, and osteopontin and reversed the decrease in binding of myocardin to the SM α-actin promoter caused by 24 h of hypoxia exposure. Thus, our results suggest that ILK initiates the phenotypic transition of PASMCs. The underlying mechanism may involve hypoxia downregulating ILK kinase activity and protein expression, causing Elk-1 to compete with myocardin for binding to the SM α-actin promoter, which downregulates the expression of the downstream target myocardin and results in the phenotypic transition of PASMCs from a contractile to a synthetic phenotype. This may be an important mechanism in the development of HPH.

MiR-15a Functions as a Diagnostic Biomarker for Coronary Artery Disease.

BACKGROUND: The present study aimed to explore the diagnostic value of miR-15a in coronary artery disease (CAD). METHODS: After recruiting all the participants, peripheral blood samples were obtained according to the instructions. miR-15a expression was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and IL-6, TNF-α, and hs-CRP expressions were detected using ELISA kits. RESULTS: The results elucidated a significantly decreased expression of miR-15a in peripheral blood samples from CAD patients compared to non-CAD controls (p < 0.01). Meanwhile, miR-15a expression was negatively correlated with LDL-C and Gensini score (p = 0.0059, 0.0243, respectively). Moreover, miR-15a expression was negatively correlated with inflammatory cytokines IL-6, TNF-α, and hs-CRP (p = 0.0009, 0.0178, 0.0005, respectively). The receiver operating curve (ROC) curve analysis demonstrated that miR-15a was a promising biomarker for early diagnosis of CAD with an area under the curve (AUC) of 0.9368. CONCLUSIONS: The present study elucidated a decreased miR-15a expression in CAD patients and showed negative correlations with LDL-C, Gensini score, and inflammatory cytokines. miR-15a may serve as a promising biomarker for early diagnosis of CAD.

miR-142 is a Sensitive Biomarker for the Diagnosis and Prognosis of Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is myocardial necrosis caused by acute and persistent ischemia and hypoxia of coronary arteries. AMI is one of the most common diseases in European countries and over 1.5 million AMI patients die of it in the United States annually. A collection of studies proposed that certain micro-RNAs play crucial roles in the onset and development of AMI. METHODS: Ninety-four AMI patients and 83 non-AMI healthy controls were recruited from Zhongda Hospital, Southeast University between July 2015 and September 2017. Serum samples were collected at admission and the expression of miR-142 was detected using real-time quantitative polymerase chain reaction (RT-qPCR) assays. RESULTS: miR-142 expression was markedly elevated in serum samples of AMI patients compared with the 83 non-AMI healthy controls. miR-142 expression was positively correlated with creatine kinase-KB (CK-MB; r = 0.6731, p = 0.0021) and troponin (r = 0.7138, p = 0.0013). The area under the curve (AUC) of miR-142, CK-MB, and troponin for the diagnosis of AMI were 0.9185, 0.8172, and 0.8717, respectively. Overall survival analysis implied that high miR-142 expression may predict poor survival (log-rank test, p = 0.0146). CONCLUSIONS: miR-142 may be a diagnostic and prognostic indicator for AMI, and therefore, it may contribute to AMI clinicopathologic prediction.

High triglyceride-glucose index is associated with poor prognosis in patients with acute ST-elevation myocardial infarction after percutaneous coronary intervention.

BACKGROUND: Insulin resistance (IR) is considered a pivotal risk factor for cardiometabolic diseases, and the triglyceride-glucose index (TyG index) has emerged as a reliable surrogate marker of IR. Although several recent studies have shown the association of the TyG index with vascular disease, no studies have further investigated the role of the TyG index in acute ST-elevation myocardial infarction (STEMI). The objective of the present study was to evaluate the potential role of the TyG index as a predictor of prognosis in STEMI patients after percutaneous coronary intervention (PCI). METHODS: The study included 1092 STEMI patients who underwent PCI. The patients were divided into 4 quartiles according to TyG index levels. Clinical characteristics, fasting plasma glucose (FPG), triglycerides (TGs), other biochemical parameters, and the incidence of major adverse cardiovascular and cerebral events (MACCEs) during the follow-up period were recorded. The TyG index was calculated using the following formula: ln[fasting TGs (mg/dL) × FPG (mg/dL)/2]. RESULTS: The incidence of MACCEs and all-cause mortality within 30 days, 6 months and 1 year after PCI were higher among STEMI patients with TyG index levels in the highest quartile. The TyG index was significantly associated with an increased risk of MACCEs in STEMI patients within 1 year after PCI, independent of confounding factors, with a value of 1.529 (95% CI 1.001-2.061; P = 0.003) for those in the highest quartile. The area under the curve (AUC) of the TyG index predicting the occurrence of MACCEs in STEMI patients after PCI was 0.685 (95% CI 0.610-0.761; P = 0.001). The results also revealed that Killip class > 1, anaemia, albumin, uric acid, number of stents and left ventricular ejection fraction (LVEF) were independent predictors of MACCEs in STEMI patients after PCI (all P < 0.05). CONCLUSIONS: This study indicated an association between higher TyG index levels and increased risk of MACCEs in STEMI patients for the first time, and the TyG index might be a valid predictor of clinical outcomes in STEMI patients undergoing PCI. Trial Registration ChiCTR1900024577.

Baicalin Suppresses the Proliferation and Migration of Ox-LDL-VSMCs in Atherosclerosis through Upregulating miR-126-5p.

Atherosclerosis (AS) is a chronic inflammatory disease threatening human health, and vascular smooth muscle cells (VSMCs) are involved in AS processes. Baicalin is a flavonoid compound, which has anti-atherosclerotic effect. The aim of our study was to explore the molecular mechanism of baicalin on AS. The expression of miR-126-5p was measured in peripheral blood of AS patients and healthy control. We found miR-126-5p expression was decreased in AS. Then, high-mobility group box 1 (HMGB1) was verified as a target of miR-126-5p and its expression was increased in AS. Similarly, miR-126-5p and HMGB1 expression was downregulated and upregulated in oxidized low-density lipoprotein treated VSMCs (ox-LDL-VSMCs), respectively. Furthermore, baicalin upregulated miR-126-5p and downregulated HMGB1 expression. Functionally, baicalin significantly inhibited ox-LDL-VSMCs proliferation and migration, and miR-126-5p targets HMGB1 to enhance the inhibition induced by baicalin. Taken together, baicalin is able to prevent AS, which suppressed the proliferation and migration of ox-LDL-VSMCs through upregulating miR-126-5p by targeting HMGB1. These findings suggested that baicalin is an effective drug to alleviate AS, and miR-126-5p is a novel therapeutic target for AS.

Down-regulation of lncRNA MEG3 promotes hypoxia-induced human pulmonary artery smooth muscle cell proliferation and migration via repressing PTEN by sponging miR-21.

Hypoxia-induced pulmonary hypertension is a life-threatening disease arising from a progressive increase in pulmonary vascular resistance, irreversible pulmonary vascular remodeling and resulting in right ventricular failure. Recent studies suggested that pulmonary artery smooth muscle cell proliferation and migration played an important role in the pathogenesis of hypoxia-induced pulmonary hypertension. However, the mechanisms of hypoxia-induced pulmonary hypertension are complicated and largely unclear. In this study, we discovered that lncRNA MEG3 was down-regulated in human pulmonary artery smooth muscle cell in hypoxia, and inhibition of MEG3 promoted the cell proliferation and cell migration in both normal and hypoxia condition. Further study demonstrated that MEG3 exerted its function via regulation of miR-21 expression in both normal and hypoxia condition. In addition, we displayed the modulation of PTEN by miR-21 and their role in hypoxia. Ultimately, our study illustrated that MEG3 exerts its role via miR-21/PTEN axis in human pulmonary artery smooth muscle cell under both normal and hypoxia conditions.

Kir2.1 regulates rat smooth muscle cell proliferation, migration, and post-injury carotid neointimal formation.

Phenotype switching of vascular smooth muscle cells (VSMC) from the contractile type to the synthetic type is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. Inward rectifier K(+) channel 2.1 (Kir2.1) has been identified in VSMC. However, whether it plays a functional role in regulating cellular transformation remains obscure. In this study, we evaluated the role of Kir2.1 on VSMC proliferation, migration, phenotype switching, and post-injury carotid neointimal formation. Kir2.1 knockdown significantly suppressed platelet-derived growth factor BB-stimulated rat vascular smooth muscle cells (rat-VSMC) proliferation and migration. Deficiency in Kir2.1 contributed to the restoration of smooth muscle α-actin, smooth muscle 22α, and calponin and to a reduction in osteopontin expression in rat-VSMC. Moreover, the in vivo study showed that rat-VSMC switched to proliferative phenotypes and that knockdown of Kir2.1 significantly inhibited neointimal formation after rat carotid injury. Kir2.1 may be a potential therapeutic target in the treatment of cardiovascular diseases, such as atherosclerosis and restenosis following percutaneous coronary intervention.

SERCA2a was serotonylated and may regulate sino-atrial node pacemaker activity.

The modulation of sino-atrial node (SAN) automaticity is an essential mechanism of heart rate generation that is still not completely understood. Recent studies highlighted the importance of protein serotonylation by intracellular 5-HT during varies physiological actions. Nevertheless, the functional role of protein serotonylation in controlling SAN automaticity is largely unexplored. In this study, we screened the cardiomyocytes proteins and found that sarco(endo)plasmic reticulum Ca ATPase type 2a (SERCA2a) can be serotonylated. Simulation studies using mathematical SAN cell model showed that variation of Ca2+ affinity of SERCA2a pump cause either tachycardia or bradycardia.