Cellular repressor of E1A-stimulated genes (CREG) is a recently discovered secreted glycoprotein involved in homeostatic modulation. We previously reported that CREG is abundantly expressed in the adult vascular endothelium and dramatically downregulated in atherosclerotic lesions. In addition, CREG participates in the regulation of apoptosis, inflammation and wound healing of vascular endothelial cells. In the present study, we attempted to investigate the effect of CREG on the proliferation of vascular endothelial cells and to decipher the underlying molecular mechanisms. Overexpression of CREG in human umbilical vein endothelial cells (HUVEC) was obtained by infection with adenovirus carrying CREG. HUVEC proliferation was investigated by flow cytometry and 5-bromo-2'-deoxy-uridine (BrdU) incorporation assays. The expressions of cyclins, cyclin-dependent kinases and signaling molecules were also examined. In CREG-overexpressing cells, we observed a marked increase in the proportion of the S and G2 population and a decrease in the G0/G1 phase population. The number of BrdU positively-stained cells also increased, obviously. Furthermore, silencing of CREG expression by specific short hairpin RNA effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVEC). CREG overexpression induced the expression of cyclin E in both protein and mRNA levels to regulate cell cycle progression. Further investigation using inhibitor blocking analysis identified that ERK activation mediated the CREG modulation of the proliferation and cyclin E expression in HUVEC. In addition, blocking vascular endothelial growth factor (VEGF) in CREG-overexpressed HUVEC and supplementation of VEGF in CREG knocked-down HUVEC identified that the pro-proliferative effect of CREG was partially mediated by VEGF-induced ERK/cyclin E activation. These results suggest a novel role of CREG to promote HUVEC proliferation through the ERK/cyclin E signaling pathway.
1 November 2023 in Frontiers in Cardiovascular Medicine
Background and objective: This study aimed to assess the efficacy and safety of “one-stop” procedures that combined radiofrequency catheter ablation and left atrial appendage closure (LAAC) with the Watchman device under the guidance of intracardiac echocardiography (ICE) vs. transesophageal echocardiography (TEE) in patients with atrial fibrillation.Methods and results: In this study, we prospectively enrolled patients who underwent “one-stop” procedures under the guidance of ICE (n = 193, 109 men, 65.02 ± 8.47 years) or TEE (n = 109, 69 men, 64.23 ± 7.75 years) between January 2021 and October 2022. Intraprocedural thrombus formation in the left atrial appendage (LAA) was observed in 3 (1.46%) patients in the ICE group and 15 (11.63%) patients in the TEE group (P < 0.05) before LAAC. Total fluoroscopy time and dose in the ICE group were less than those in the TEE group. The total “one-stop” turnaround time and LAAC procedure time in the ICE group were significantly shorter than those in the TEE group (P < 0.05). Postoperative esophagus discomfort, nausea and vomiting, and hypotension were more often seen in the TEE group (P < 0.001). There was no significant difference in matched cases between ICE and fluoroscopy measurements (P = 0.082). The TEE results related to LAAC and clinical events were similar between the two groups during the follow-up (P > 0.05).Conclusion: The ICE-guided “one-stop” procedure was safe and feasible with less radiation exposure, shorter turnaround time, and fewer complications and intraoperative thrombus formations than the TEE group. ICE offered accurate measurements in the LAA dimension during LAAC. Echocardiography during the “one-stop” procedures was necessary to rule out the intraoperative thrombus.
27 October 2023 in Cardiology Research and Practice
Background. Bachmann’s bundle (BB) is the main pathway of interatrial connection that could be involved in the development of atrial fibrillation (AF). Based on this hypothesis, we raised a novel ablation strategy, BB modification in addition to circumferential pulmonary vein isolation (CPVI-BB) in patients with AF. Methods. A retrospective cohort of patients with AF who underwent CPVI-BB or CPVI alone from March 2018 to July 2021 was enrolled in our study. Propensity score matching was performed in patients with paroxysmal AF and persistent AF, respectively, to reduce the risk of selection bias between the treatment strategies (CPVI-BB or CPVI alone). The primary endpoint was overall freedom from atrial arrhythmia recurrence through 12 months of follow-up. Results. Our propensity score-matched cohort included 82 patients with paroxysmal AF (CPVI group: n = 41; CPVI-BB group: n = 41) and 168 patients with persistent AF (CPVI group: n = 84; CPVI-BB group: n = 84). Among patients with persistent AF, one-year freedom from atrial arrhythmia recurrence rate was 83.3% in the CPVI-BB group and 70.2% in the CPVI group (log-rank = 0.047). Among patients with paroxysmal AF, no significant difference was found in the primary endpoint between two groups (85.4% in the CPVI-BB group vs. 80.5% in the CPVI group; log-rank = 0.581). In addition, procedure-related complications and recurrence of atrial tachycardia or atrial flutter were similar between the two treatment groups, regardless of the type of AF. Conclusions. BB modification in addition to CPVI is an effective approach in increasing the maintenance of sinus rhythm in patients with persistent AF, while it does not improve the clinical outcomes of radiofrequency catheter ablation in patients with paroxysmal AF.
(1) Background: Atrial scars play an important role in atrial tachycardia (AT). They can not only be found in patients with prior cardiac surgery (PCS) but also in patients without PCS or significant structural heart disease, in which case the scar is called a spontaneous scar (SS). This study aims to compare the characteristics, mechanisms and ablation outcomes of AT in patients with PCS and SS. (2) Methods: We retrospectively reviewed electrophysiological and ablative characteristics of ATs in 46 patients with PCS and 18 patients with SS. (3) Results: There were averages of 1.52 and 2.33 ATs per patient in the PCS group and SS group, respectively (p < 0.01). Cavo-tricuspid isthmus dependent atrial flutter (CTI-AFL) was presented in most patients in both groups (93.50% vs. 77.80%, p = 0.17), whereas the SS group had a higher occurrence of scar-mediated reentrant AT (SMAT) and focal AT (FAT) compared with the PCS group (88.90% vs. 39.10%, p < 0.01; 22.2% vs. 2.2%, p < 0.05). There were no significant differences in acute success rate between the two groups, whereas patients with SS had lower long-term success rate (87.0% vs. 61.1%, p < 0.05) and higher occurrence of sinus node dysfunction (SND) (4.3% vs. 22.2%, p < 0.05). (4) Conclusions: CTI-AFL is common in both patients with PCS and SS, and routine CTI ablation is recommended. Compared with patients with PCS, patients with SS have more ATs, especially with higher occurrence of SMAT and FAT, and had a lower long-term success rate and higher incidence of SND.