Jie Qiu

Pulmonary vascular remodeling, characterized by the thickening of all three layers of the blood vessel wall, plays a central role in the pathogenesis of pulmonary hypertension (PH). Despite the approval of several drugs for PH treatment, their long-term therapeutic effect remains unsatisfactory, as they mainly focus on vasodilation rather than addressing vascular remodeling. Therefore, there is an urgent need for novel therapeutic targets in the treatment of PH. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a vital transcription factor that regulates endogenous antioxidant defense and emerges as a novel regulator of pulmonary vascular remodeling. Growing evidence has suggested an involvement of Nrf2 and its downstream transcriptional target in the process of pulmonary vascular remodeling. Pharmacologically targeting Nrf2 has demonstrated beneficial effects in various diseases, and several Nrf2 inducers are currently undergoing clinical trials. However, the exact potential and mechanism of Nrf2 as a therapeutic target in PH remain unknown. Thus, this review article aims to comprehensively explore the role and mechanism of Nrf2 in pulmonary vascular remodeling associated with PH. Additionally, we provide a summary of Nrf2 inducers that have shown therapeutic potential in addressing the underlying vascular remodeling processes in PH. Although Nrf2-related therapies hold great promise, further research is necessary before their clinical implementation can be fully realized.

Pulsed field ablation (PFA) is a new ablative method for the therapy of arrhythmia. Recent preclinical and clinical studies have already demonstrated the feasibility and safety of PFA for the treatment of atrial fibrillation (AF). However, the application of PFA may not be limited to the above fields. There are some data on the application of PFA on ventricular arrhythmias (VAs), such as ventricular fibrillation (VF) and ventricular tachycardia (VT). Further, a case report about PFA has been published recently, in which PFA was successfully applied to the ablation of premature ventricular contractions (PVCs) from the right ventricular outflow tract. Thus, we aimed to review recent research findings of PFA in ventricular ablation and evaluate the possibility of its application in VAs.

Background: Focal atrial tachycardia (AT) originating from the right atrial appendage (RAA), often persistent and refractory, is clinically rare in pregnant woman, and the therapy is much more challenging. We report that a pregnant woman presented with hypotension due to persistent and refractory atrial tachycardia and was successfully cured by a multidisciplinary treatment (MDT) approach, consisting of a combination of zero-fluoroscopy mapping and thoracoscopic atrial appendectomy. We also carried out a literature review of this topic. Methods and Results: A 26-year-old woman in pregnancy at 21 weeks presented with severe palpitation and hypotension due to persistent rapid supraventricular tachycardia (SVT). Since adenosine triphosphate could not terminate the tachycardia, a catheter ablation procedure was planned and finally canceled when the zero-fluoroscopy mapping using Carto 3^TM system revealed an atrial tachycardia originating from the RAA. Thoracoscopic RAA ectomy was recommended after multidisciplinary consultation and successfully performed without fluoroscopy. Ensite^TM velocity mapping system was used for accurately locating the origin of the arrhythmia during ectomy. The woman finally produced a healthy baby during follow-up. Conclusions: Focal AT originating from appendage in pregnant patients can be persistent, refractory, and life-threatening; traditional strategies, such as medicine or catheter ablation, are limited in this situation. MDT measures, using a thoracoscopic ectomy and zero-fluoroscopy three-dimensional electroanatomical mapping technique, is minimally invasive and a promising strategy.

Caveolin-3 is a muscle-specific protein on the membrane of myocytes correlated with a variety of cardiovascular diseases. It is now clear that the caveolin-3 plays a critical role in the cardiovascular system and a significant role in cardiac protective signaling. Mutations in the gene encoding caveolin-3 cause a broad spectrum of clinical phenotypes, ranging from persistent elevations in the serum levels of creatine kinase in asymptomatic humans to cardiomyopathy. The influence of Caveolin-3(CAV-3) mutations on current density parallels the effect on channel trafficking. For example, mutations in the CAV-3 gene promote ventricular arrhythmogenesis in long QT syndrome 9 by a combined decrease in the loss of the inward rectifier current (I_K1) and gain of the late sodium current (I_Na-L). The functional significance of the caveolin-3 has proved that caveolin-3 overexpression or knockdown contributes to the occurrence and development of arrhythmias. Caveolin-3 overexpression could lead to reduced diastolic spontaneous Ca²⁺ waves, thus leading to the abnormal L-Type calcium channel current-induced ventricular arrhythmias. Moreover, CAV-3 knockdown resulted in a shift to more negative values in the hyperpolarization-activated cyclic nucleotide channel 4 current (I_HCN4) activation curve and a significant decrease in I_HCN4 whole-cell current density. Recent evidence indicates that caveolin-3 plays a significant role in adipose tissue and is related to obesity development. The role of caveolin-3 in glucose homeostasis has attracted increasing attention. This review highlights the underlining mechanisms of caveolin-3 in arrhythmia. Progress in this field may contribute to novel therapeutic approaches for patients prone to developing arrhythmia.