Association between triglyceride glucose index, coronary artery calcification and multivessel coronary disease in Chinese patients with acute coronary syndrome.

BACKGROUND: Multivessel coronary disease (MVCD) is the common type of coronary artery disease in acute coronary syndrome (ACS). Coronary artery calcification (CAC) has been confirmed the strong predictor of major adverse cardiovascular events (MACEs). Several studies have validated that triglyceride glucose (TyG) index can reflect the degree of coronary calcification or predict MACEs. However, no evidence to date has elucidated and compared the predictive intensity of TyG index or/and coronary artery calcification score (CACS) on multi-vascular disease and MACEs in ACS patients. METHODS: A total of 935 patients, diagnosed with ACS and experienced coronary computed tomography angiography (CCTA) from August 2015 to March 2022 in the Second Hospital of Shandong University, were selected for retrospective analysis. The subjects were divided into TyG index quartile 1-4 groups (Q1-Q4 groups), non-multivessel coronary disease (non-MVCD) and multivessel coronary disease (MVCD) groups, respectively. The general data, past medical or medication history, laboratory indicators, cardiac color Doppler ultrasound, CACS, and TyG indexes were respectively compared among these groups. The ROC curve preliminarily calculated and analyzed the diagnostic value of TyG index, CACS, and the combination of the two indicators for MVCD. Univariate and multivariate logistic regression analysis discriminated the independent hazard factors for forecasting MVCD. RESULTS: Compared with the lower TyG index and non-MVCD groups, the higher TyG index and MVCD groups had higher values of age, smoking history, waist circumference, systolic blood pressure, low-density lipoprotein cholesterol(LDL-C), fasting blood glucose and glycosylated hemoglobin, and CACS, but lower values of high-density lipoprotein cholesterol(HDL-C) (all P < 0.01). Coronary artery calcification is more common in the left anterior descending artery. Compared with non-MVCD, each unit increase in TyG index was associated with a 1.213-fold increased risk of MVCD. Logistic regression analysis adjusted for potential confounders indicated that TyG index is an independent risk factor for MVCD. With the increase of TyG index, the incidence of MACEs, apart from all-cause death, cardiac death, unexpected re-hospitalization of heart failure, recurrent ACS or unplanned revascularization, and non-fatal stroke in coronary artery increased (P log-rank < 0.001). CONCLUSION: TyG index could completely substitute for CACS as a reliable, practical, and independent indicator for predicting the severity and prognosis of MVCD in patients with ACS.

Chemerin-induced angiogenesis and adipogenesis in 3 T3-L1 preadipocytes is mediated by lncRNA Meg3 through regulating Dickkopf-3 by sponging miR-217.

PURPOSE: Obesity is often caused by the excess adipogenesis and regulated by long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We performed this study to investigate the influence of Meg3 expression on adipogenesis and also the Meg3/miR-217/Dkk3 axis-mediated molecular mechanism in adipogenesis and angiogenesis. METHODS: 3 T3-L1 preadipocytes were incubated with chemerin and transfected with Meg3-overexpressing (OE-Meg3) and Dkk3-overexpressing (OE-Dkk3) plasmids, siRNAs, and miR-217 mimics, inhibitor and scrambled sequences for 48 h or 72 h. The changes in cell proliferation, adipogenesis and angiogenesis ability in 3 T3-L1 preadipocytes was detected by using the corresponding assay. The expressions of related proteins were detected via western blot. RESULTS: Chemerin decreased miR-217 expression and increased Meg3 expression, meanwhile promoted the proliferation, adipogenesis and angiogenesis in 3 T3-L1 preadipocytes. Besides, OE-Meg3 exerted the synergistic effect on 3 T3-L1 preadipocytes when co-treated with chemerin. The target interactions between Meg3 and miR-217 as well as between miR-217 and Dkk3 were validated using dual-luciferase reporter system. SiMeg3 antagonized chemerin-induced changes, while the addition of miR-217 inhibitor attenuated siMeg3-induced changes in 3 T3-L1 preadipocytes. The proliferation, adipogenesis and angiogenesis in 3 T3-L1 preadipocytes were suppressed by miR-217 mimics, while promoted by the OE-Dkk3 Chemerin promoted the expression of fatty acid binding protein 4 and vascular endothelial growth factor (VEGF) proteins, and decreased the expression of cyclin D1, c-Myc, and ß-catenin proteins. Meanwhile, these effects were further enhanced by OE-Meg3 or OE-Dkk3. However, the transfection of siMeg3, or miR-217 mimics, or siDkk3 reversed the previous changes. CONCLUSIONS: Meg3/miR-217/Dkk3 induced adipogenesis and angiogenesis in 3 T3-L1 preadipocytes via activating VEGF signaling pathway and inhibiting Wnt/ß-catenin signaling pathway.

Genetic Predisposition of Both Waist Circumference and Hip Circumference Increased the Risk of Venous Thromboembolism.

BACKGROUND: Obesity, especially abdominal obesity, is an independent indicator of increased cardiovascular risk. Observational studies have shown an observational association between obesity and venous thromboembolism (VTE). As a type of VTE, pulmonary embolism (PE) is also associated with obesity. However, it is unclear whether the observed associations are causal or caused by confounding bias or reverse causality. METHODS: We performed a two-sample test by obtaining the exposure dataset of waist circumference (WC) and hip circumference (HC) from the Neale Laboratory Consortium's genome-wide association study summary data and the summary-level outcome data of VTE and PE from FinnGen Biobank of European ancestry to determine the causal effect of WC and HC on VTE and PE. RESULTS: All three Mendelian randomization methods displayed a positive association between WC/HC and VTE/PE. WC and HC were positively associated with VTE (odds ratio [OR] = 1.803 per 1 standard deviation [SD] increase in WC, 95% confidence interval [CI] = 1.393-2.333; p < 0.001; OR = 1.479 per 1 SD increase in HC, 95% CI = 1.219-1.796; p < 0.001, respectively). Furthermore, we found a causal association between genetically predicted WC/HC and a higher risk of PE (OR = 1.929 per 1 SD increase in WC, 95% CI = 1.339-2.778, p < 0.001; OR = 1.431 per 1 SD increase in HC, 95% CI =1.095-1.869; p = 0.009, respectively). CONCLUSION: There is a significant causal relationship between WC/HC and VTE/PE, which is consistent with observational studies. Taking measures to reduce WC/HC of obesity may help reduce the incidence of VTE/PE.