BACKGROUND: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism. METHODS: Protein S-sulfhydration in endothelial cells (ECs) during AAD was detected and hub genes regulating homeostasis of the endothelium were identified. Clinical data of patients with AAD and healthy controls were collected, and the level of the cystathionine γ lyase (CSE)/hydrogen sulfide (H 2 S) system in plasma and aortic tissue were determined. Mice with EC-specific CSE deletion or overexpression were generated, and the progression of AAD was determined. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to determine the upstream regulators of the CSE/H 2 S system and the findings were confirmed in transgenic mice. RESULTS: Higher plasma H 2 S levels were associated with a lower risk of AAD, after adjustment for common risk factors. CSE was reduced in the endothelium of AAD mouse and aorta of patients with AAD. Protein S-sulfhydration was reduced in the endothelium during AAD and protein disulfide isomerase (PDI) was the main target. S-sulfhydration of PDI at Cys343 and Cys400 enhanced PDI activity and mitigated endoplasmic reticulum stress. EC-specific CSE deletion was exacerbated, and EC-specific overexpression of CSE alleviated the progression of AAD through regulating the S-sulfhydration of PDI. ZEB2 (zinc finger E-box binding homeobox 2) recruited the HDAC1-NuRD complex (histone deacetylase 1–nucleosome remodeling and deacetylase) to repress the transcription of CTH , the gene encoding CSE, and inhibited PDI S-sulfhydration. EC-specific HDAC1 deletion increased PDI S-sulfhydration and alleviated AAD. Increasing PDI S-sulfhydration with the H 2 S donor GYY4137 or pharmacologically inhibiting HDAC1 activity with entinostat alleviated the progression of AAD. CONCLUSIONS: Decreased plasma H 2 S levels are associated with an increased risk of aortic dissection. The endothelial ZEB2-HDAC1-NuRD complex transcriptionally represses CTH , impairs PDI S-sulfhydration, and drives AAD. The regulation of this pathway effectively prevents AAD progression.

Background: Left subclavian artery revascularization (LSA) is frequently performed in the setting of thoracic endovascular repair (TEVAR). The purpose of this study was to compare different techniques for LSA revascularization during TEVAR.Methods: We performed a single center’s retrospective cohort study from 2016 to 2019. Patients were categorized by LSA revascularization methods, including direct coverage without revascularization (Unrevascularized), carotid-subclavian bypass (CSB), fenestrated TEVAR (F-TEVAR). Indications, demographics, operation details, and outcomes were analyzed using standard statistical analysis.Results: 171 patients underwent TEVAR with LSA coverage, 16.4% (n=28) were unrevascularized and the remaining patients underwent CSB (n=100 [58.5%]) or F-TEVAR (n=43 [25.1%]). Demographics were similar between the unrevascularized and revascularized groups, except for procedure urgent status (p = 0.005). The incidence of postoperative spinal cord ischemia was significantly higher between unrevascularized and revascularized group (10.7% vs 1.4%; p = 0.032). There was no difference in 30-day and mid-term rates of mortality, stroke, and left upper extremity ischemia. CSB was more likely time-consuming than F-TEVAR [3.25 (2.83 - 4) vs 2 (1.67 – 2.67) hours, p = 0], but there were no statistically significant differences in 30-day or midterm outcomes for CSB vs F-TEVAR. During a mean follow-up time of 24.8 months, estimates survival rates had no difference.Conclusions: LSA revascularization in zone 2 TEVAR is necessary which is associated with a low 30-day rate of spinal cord ischemia. When LSA revascularization is required during TEVAR, CSB and F-TEVAR are all safe and effective methods, and F-TEVAR appears to offer equivalent clinical outcomes as a less time-consuming and minimally invasive alternative.

Background: Cannulation strategy in surgery for acute type A aortic dissection (ATAAD) remains controversial. We aimed to retrospectively analyze the safety and efficacy of double arterial cannulation (DAC) compared with right axillary cannulation (RAC) for ATAAD.Methods: From January 2016 to December 2018, 431 ATAAD patients were enrolled in the study. Patients were divided into DAC group (n=341) and RAC group (n=90). Propensity score matching analysis was performed to compare the early and mid-term outcomes between these two groups. To confirm the organ protection effect by DAC, intraoperative blood gas results and cardiopulmonary bypass parameters were compared between the two groups.Results: Demographics and preoperative comorbidities were comparable between two groups, while patients in DAC group were younger than RAC group (51.55±13.21 vs. 56.07±12.16 years, P＜0.001 ) . DAC had a higher incidence of limb malperfusion (18.2% vs. 10.0%, P=0.063) and lower incidence of coronary malperfusion (5.3% vs. 12.2%, P=0.019). No significant difference in cardiopulmonary bypass and cross-clamp time was found between the two groups. The in-hospital mortality was 13.5% (58/431), while there was no difference between the two groups (13.5% vs. 13.3%; P=0.969). Patients who underwent DAC had higher incidence of postoperative stroke (5.9% vs. 0%, P=0.019) and lower incidence of postoperative acute kidney injury (AKI) (24.7% vs. 40.3%; P=0.015). During a mean follow-up period of 31.8 (interquartile range, 25-45) months, the overall survival was 81.5% for DAC group and 78.0% for RAC group (P=0.560). Intraoperative blood gas results and cardiopulmonary bypass parameters showed that DAC group had more intraoperative urine output volume than RAC group (P=0.05), and the time of cooling (P=0.04) and rewarming (P=0.04) were shorter in DAC group.Conclusions: DAC will not increase the surgical risks compared to RAC, but could reduce the incidence of postoperative AKI which may be benefit for renal protection.