Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis.

BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. CONCLUSION: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.

Corrigendum to "Safety and efficacy of ablation index-guided high-power ablation for the treatment of atrial fibrillation" [Heliyon 9 (4), (April 2023) Article e15311].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15311.].

Safety and efficacy of ablation index-guided high-power ablation for the treatment of atrial fibrillation.

Objective: To study the safety and efficacy of high-power ablation for atrial fibrillation (AF) guided by lesion size index (LSI) and impedance cutoff. Method: A total of 223 patients who underwent radiofrequency catheter ablation of atrial fibrillation (including paroxyparal atrial fibrillation and persistent atrial fibrillation) in the Department of Cardiology of Anhui Provincial Hospital from February 2019 to July 2020 were enrolled, and were divided into 123 patients in the high-power ablation group (HPAI) and 100 patients in the conventional power ablation group (CPAI). The HPAI group adopted high-power (40-50 W) ablation by impedance cutoff, and the CPAI group adopted conventional-power (30-35 W) ablation. Patients in both groups were ablated guided by the same LSI. For both groups, we analyzed the pulmonary vein single-circle isolation rate, ablation time, X-ray exposure, impedance drop value, incidence of complications, and recurrence rate within one year after operation. Results: There was no significant difference in the success rate of pulmonary vein single-circle isolation, X-ray perspective time, and X-ray exposure quantity between the HPAI group and the CPAI group (88.60% vs 82.00%, P = 0.161; 8.7 ± 3.74 min vs 7.82 ± 3.86 min, P = 0.067; 54.74 ± 28 min vs 52.78 ± 39.58 min, P = 0.139); the annular pulmonary vein ablation time and total ablation time were less in the HPAI group (35.74 ± 7.25 min vs 65.49 ± 7.34 min, P < 0.01; 55.42 ± 11.61 min vs 76.9 ± 6.79 min, P < 0.01); the impedance drop values at 10-15Ω and 15-20Ω were higher in the HPAI group (25.3% vs 19.1%, P < 0.05; 24.1% vs 19.1%, P < 0.05); there was no significant difference in the recurrence rate within one year after operation between the two groups; and no serious complications occurred in the two groups. Conclusion: High-power ablation guided by LSI and impedance cutoff could significantly shorten the AF ablation time and reduce complications.

LncRNA HOXA11-AS promotes vascular endothelial cell injury in atherosclerosis by regulating the miR-515-5p/ROCK1 axis.

AIMS: Long non-coding RNA HOXA11-AS participated in heart disease. In this study, we aim to evaluate the potential roles of HOXA11-AS in atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: The expression levels of HOXA11-AS in ox-LDL-treated HUVECs and arch tissues of high-fat diet-fed ApoE-/- mice (n = 10) were assessed by qRT-PCR. The effects of HOXA11-AS knockdown on the development of atherosclerosis were evaluated using in vitro and in vivo models. Luciferase reporter and RNA immunoprecipitation (RIP) assays verified the potential relationships between HOXA11-AS or ROCK1 and miR-515-5p. The interactive roles between HOXA11-AS and miR-515-5p and between miR-515-5p and ROCK1 were further characterized in ox-LDL-treated HUVECs. Our data showed that HOXA11-AS was significantly up-regulated (P < 0.001), whereas miR-515-5p was dramatically down-regulated in AS mice tissues (P < 0.001) and ox-LDL-treated HUVECs (P < 0.01). Ox-LDL could induce endothelial injuries by inhibiting cell proliferation (P < 0.001) and SOD synthesis (P < 0.001), promoting apoptosis (P < 0.01), ROS (P < 0.001), and MDA production (P < 0.001), increasing Bax (P < 0.001) and cleaved Caspase-3 (P < 0.001), and decreasing Bcl-2 (P < 0.001) and phosphorylated eNOS (P < 0.01). HOXA11-AS knockdown attenuated endothelial injuries via increasing eNOS phosphorylation. Luciferase assay and RIP results confirmed that miR-515-5p is directly bound to HOXA11-AS and ROCK1. HOXA11-AS promoted ox-LDL-induced HUVECs injury by directly inhibiting miR-515-5p from increasing ROCK1 expression and subsequently decreasing the expression and phosphorylation of eNOS. MiR-515-5p mimics could partially reverse the effects of HOXA11-AS knockdown. CONCLUSIONS: HOXA11-AS contributed to atherosclerotic injuries by directly regulating the miR-515-5p/ROCK1 axis. This study provided new evidence that HOXA11-AS might be a candidate for atherosclerosis therapy.

A 6 hour therapeutic window, optimal for interventions targeting AMPK synergism and apoptosis antagonism, for cardioprotection against myocardial ischemic injury: an experimental study on rats.

The time relation between autophagy and myocardium ischemia (MI) has never been documented. Therefore, the present study was conducted to find out the exact timings and specific roles that AMP-activated protein kinase (AMPK)-mTOR signaling pathway plays on autophagy and apoptosis in rats' ischemic heart. 36 male Sprague Dawley (SD) rats were divided randomly into control and MI groups (each = 6). MI models were created by ligating left anterior descending artery (LAD) of rat hearts and the right myocardium were harvested at 0.5 h, 1 h, 3 h, 6 h, 12 h after ischimia. Expressions of Phosphorylated-AMPK (p-AMPK) and Phosphorylated-mTOR (p-mTOR) were determined by immunohistochemistry (IHC), western blotting (WB) and quantitative real-time PCR (Q-PCR) methods. LC3 expression was determined by WB and Q-PCR. The level of cell apoptosis was measured by the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) method. p-AMPK was activated significantly in ischemic myocardium and its expression at MI groups showed a time dependent pattern with a fluctuating pattern compared to the control group. p-AMPK levels were seen to rise at 0.5 h followed by a fall at 1 h after MI, which again gradually peaked at 6 h and finally decreased at 12 h. While, p-mTOR levels suggested a constant declining trend with time. Autophagy related protein LC3 had a sustained up-regulation with time. TUNEL method suggested that apoptosis increased at 0.5 h, then decreased at 1 h and 3 h after MI and finally showed a continuous rising trend. Activation of protective autophagy that occured during the initial phases of ischemic insults was within 6 hours. When the ischemia was prolonged, after 6 hours, although autophagy increased, cardiomyocyte death followed via the activation of apoptosis. Thus, limiting autophagy within 6 hours would give us double benefits. It would prevent the death related autophagy and prevent apoptotic cellular death. This 6 hours time period could serve as a landmark for therapeutic application for achieving cardioprotection from ischemic insults.