ACE2 deficiency inhibits thoracic aortic dissection by enhancing SIRT3 mediated inhibition of inflammation and VSCMs phenotypic switch.

BACKGROUND: Thoracic aortic dissection (TAD) is an irreversible cardiovascular disorder with high mortality and morbidity. However, the molecular mechanisms remain elusive. Thus, identifying an effective therapeutic target to prevent TAD is especially critical. The purpose of this study is to elucidate the potential mechanism of inflammation and vascular smooth muscle cell (VSMCs) phenotypic switch in ß-aminopropionitrile fumarate (BAPN)-induced TAD. METHODS: A mouse model of TAD induced by BAPN and IL-1ß -stimulated HVSMCs in vivo and in vitro models, respectively. ACE2 Knockdown mice treated with BAPN or without, and the TAD mouse model was treated with or without AAV-ACE2. Transthoracic ultrasound was conducted for assessment the maximum internal diameter of the thoracic aorta arch. RNA sequencing analysis was performed to recapitulate transcriptome profile changes. Western blot were used to detect the expression of MMP2, MMP9, ACE2, SIRT3, OPN, SM22α and other inflammatory markers. The circulating levels of ACE2 was measured by ELISA assay. Histological changes of thoracic aorta tissues were assessed by H&E, EVG and IHC analysis. RESULTS: We found that circulating levels of and the protein levels of ACE2 were increased in the TAD mouse model and in patients with TAD. For further evidence, ACE2 deficiency decelerated the formation of TAD. However, overexpression of ACE2 aggravated BAPN-induced aortic injury and VSMCs phenotypic switch via lowered SIRT3 expression and elevated inflammatory cytokine expression. CONCLUSION: ACE2 deficiency prevented the development of TAD by inhibiting inflammation and VSMCs phenotypic switch in a SIRT3-dependent manner, suggesting that the ACE2/SIRT3 signaling pathway played a pivotal role in the pathological process of TAD and might be a potential therapeutical target.

Arterial dissection in scuba divers: a potential adverse manifestation of the physiological effects of immersion.

Introduction: Aortic dissections and dissections of cervical, cerebral, and coronary arteries have been previously reported in scuba divers. These incidents may be the consequence of a variety of physiological effects. We review the reported cases of arterial dissection in scuba divers and discuss potential contributing factors related to immersion and diving. Methods: Medline, CINAHL Plus, and SPORTDiscus were searched for published reports of arterial dissection and the Australasian Diving Safety Foundation fatality database was searched for additional cases from Australia. Identified cases were recorded and scrutinised for possible contributing factors. Results: Nineteen cases of arterial dissection, both fatal and non-fatal, were identified. These included cervical or intracranial artery dissection (n = 14), aortic dissection (n = 4), and coronary artery dissection (n = 1). There were 14 male and five female victims; mean age 44 years (SD 14, range 18-65). Contributing factors may include a combination of vasoconstriction and blood redistribution, untreated hypertension, increased pulse pressure, abnormal neck movement or positioning, constrictive and burdensome equipment, exercise, increased gas density and circuit resistance with concomitant elevated work of breathing, atheroma, and possibly the mammalian dive response. Conclusions: Dissecting aneurysms of the aorta or cervical, cerebral, and coronary arteries should be considered as a potential complication of scuba diving. The development of aneurysms associated with scuba diving is likely multifactorial in pathogenesis. Detailed reporting is important in the evaluation of cases. The potential role of the mammalian dive response as a contributing factor requires further evaluation.

Intimal Injury Potentially Plays a Key Role in the Formation of Carotid Artery Dissection: A Novel Animal Model Establishing.

Research on the pathophysiological mechanism of carotid artery dissection and its clinical translation is limited due to the lack of effective animal models to simulate the occurrence of this condition. Assuming that intimal injury is an important factor in the formation of carotid dissection, we established a novel method for inducing carotid dissection models by scraping the carotid intima using a fine needle. Scraping the carotid intima with fine needles can induce the rapid formation of carotid dissection. Magnetic resonance imaging and hematoxylin-eosin staining suggest the presence of false lumens and mural hematomas in the vessels. Our model-induction technique, inspired by iatrogenic catheter-induced artery dissections (carotid, coronary, aortic), significantly mimics the pathological process of clinical carotid dissection. The results suggest that mechanical injury may be a significant cause of carotid dissection and that intimal injury is a major factor in the formation of arterial dissections. This approach will provide assistance in the understanding of medically induced arterial dissection.

[Endocoronary imaging contribution in iatrogenic dissection management]. / Apport de l'imagerie endocoronaire dans la prise en charge d'une dissection iatrogène.

Iatrogenic coronary dissections are rare but potentially serious. Their management is complex, particularly if the dissection occurs without an angioplasty guide in the arterial lumen. In this context, angiography alone is insufficient, and endocoronary imaging is essential (using optical coherence or IVUS) to guide angioplasty when necessary (guide in the true lumen, coverage of the tear). We report here the case of an iatrogenic dissection of the right coronary artery treated with OFDI guiding.

Type A Aortic Dissection Following Heart Transplantation.

Cannulation strategies in aortic arch surgeries are a matter of immense discussion. Majority of time deep hypothermic circulatory arrest (DHCA) is the way out, but it does come with its set of demerits. Here we demonstrate a case with aortic arch dissection dealt with dual cannulation strategy in axillary and femoral artery without need for DHCA and ensuring complete neuroprotection of brain and spinal cord without hinderance of time factor. Inception of new ideas like this may decrease the need for DHCA and hence its drawbacks, thus decreasing the morbidity and mortality associated.

Acute aortic dissection during scuba diving.

A 60-year-old man with hypertension and dyslipidemia complained of chest pain upon ascending from a maximum depth of 27 meters while diving. After reaching the shore, his chest pain persisted, and he called an ambulance. When a physician checked him on the doctor's helicopter, his electrocardiogram (ECG) was normal, and there were no bubbles in his inferior vena cava or heart on a portable ultrasound examination. The physician still suspected that he had acute coronary syndrome instead of decompression illness; therefore, he was transported to our hospital. After arrival at the hospital, standard cardiac echography showed a flap in the ascending aorta. Immediate enhanced computed tomography revealed Stanford type A aortic dissection. The patient obtained a survival outcome after emergency surgery. To our knowledge, this is the first reported case of aortic dissection potentially associated with scuba diving. It highlights the importance of considering aortic dissection in patients with sudden-onset chest pain during physical activity. In addition, this serves as a reminder that symptoms during scuba diving are not always related to decompression. This report also suggests the usefulness of on-site ultrasound for the differential diagnosis of decompression sickness from endogenous diseases that induce chest pain. Further clinical studies of this management approach are warranted.

Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome.

Marfan syndrome (MFS) is a rare congenital disorder of the connective tissue, leading to thoracic aortic aneurysms (TAA) and dissection, among other complications. Currently, the most efficient strategy to prevent life-threatening dissection is preventive surgery. Periodic imaging applying complex techniques is required to monitor TAA progression and to guide the timing of surgical intervention. Thus, there is an acute demand for non-invasive biomarkers for diagnosis and prognosis, as well as for innovative therapeutic targets of MFS. Unraveling the intricate pathomolecular mechanisms underlying the syndrome is vital to address these needs. High-throughput platforms are particularly well-suited for this purpose, as they enable the integration of different datasets, such as transcriptomic and epigenetic profiles. In this narrative review, we summarize relevant studies investigating changes in both the coding and non-coding transcriptome and epigenome in MFS-induced TAA. The collective findings highlight the implicated pathways, such as TGF-ß signaling, extracellular matrix structure, inflammation, and mitochondrial dysfunction. Potential candidates as biomarkers, such as miR-200c, as well as therapeutic targets emerged, like Tfam, associated with mitochondrial respiration, or miR-632, stimulating endothelial-to-mesenchymal transition. While these discoveries are promising, rigorous and extensive validation in large patient cohorts is indispensable to confirm their clinical relevance and therapeutic potential.

Iron deficiency affects oxygen transport and activates HIF1 signaling pathway to regulate phenotypic transformation of VSMC in aortic dissection.

BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.

Aortic mineralization triggers the risk of acute type B aortic dissection.

BACKGROUND AND AIMS: The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating alkaline phosphatase (ALP) activity are associated with acute TBAD risk remains elusive. METHODS: Observational and Mendelian randomization (MR) studies were conducted sequentially. Using propensity score matching (1:1) by age and sex, patients with acute TBAD (n = 125) were compared with control patients (n = 125). Qualitative (score) and quantitative (volume) analyses of the TAC burden on different thoracic aortic segments were conducted using non-enhanced computed tomography. Univariate and multivariate analyses were used to identify significant independent risk factors for TBAD and TAC burden, respectively. MR was finally used to determine the causal relationship between elevated ALP activity and TBAD risk. RESULTS: The qualitative and quantitative analyses revealed that TAC burden was significantly higher in the TBAD group, except for in the ascending aortic segment (both p < 0.05). Preoperative circulating ALP was significantly elevated in the TBAD group (p < 0.001). The elevated TAC burden score on the descending thoracic aortic segment (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.37) and increased ALP activity (OR 1.03, 95% CI 1.01-1.06) was independently associated with TBAD risk. Interestingly, ALP was significantly positively associated with TAC burden, and MR analyses confirmed that ALP genetically predicted TBAD risk. CONCLUSIONS: Elevated ALP may trigger TBAD risk via the increased volume of TAC. Aortic mineralization may not protect the aorta itself.

Repair of Dissecting Aortic Aneurysm in Post-LVAD Patient.

Left ventricular assist devices (LVAD) are frequently used in the management of end-stage heart failure, especially given the limited availability of donor hearts. The latest HeartMate 3 LVAD delivers non-physiological continuous flow (CF), although the impact on the aorta is not well established. We highlight a case of aortic aneurysm formation complicated by dissection formation that necessitated high-risk re-operative surgery in a patient post CF-LVAD.

Managing Iatrogenic Aortic Dissection: Insight From 3D Holographic Imaging and CT Computational Fluid Dynamic Simulations.

Iatrogenic aortic dissection is a rare but life-threatening complication of coronary artery bypass surgery. We report a case with incidentally detected iatrogenic aortic dissection related to aorta cross-clamping that was successfully managed with watchful follow-up. The decision making was based on 3-dimensional holographic and fluid dynamic analysis guidance.

Acute Aortic Dissection After Transcatheter Aortic Valve Replacement.

Acute aortic dissection (AAD) is a rare and potentially fatal complication associated with transcatheter aortic valve replacement (TAVR). Owing to the paucity of existing institutional data, we sought to assess the incidence of postimplant AAD in patients who underwent TAVR at a single institution. All patients who underwent TAVR from 2013 to 2022 were retrospectively reviewed to identify those who possessed clinical or radiologic evidence of AAD after TAVR. Follow-up and survival data were retrieved for all included patients. A total of 4,317 patients underwent TAVR, of whom 9 (0.2%) sustained an AAD. These patients had a mean age of 80 years (range 53 to 92), mean Society of Thoracic Surgeons 30-day mortality risk of 5.7% (2.4% to 16.7%), and mean effective aortic valve area of 0.8 cm2 (0.4 to 1.5 cm2). Preoperative maximum aortic diameter was 3.9 cm (2.6 to 4 cm). Of these 9 patients, 6 (67%) showed evidence of Stanford type A dissection, whereas 3 (33%) were diagnosed with Stanford type B dissection. The most common causes of dissection were posterior annular rupture by the transcatheter valve (THV) (44%) and THV embolization or "pop-out" into the ascending aorta (22%). A total of 6 patients (66.7%), comprising 5 type A (55.6%) and 1 type B (11.1%) aortic dissections, died within 30 days of AAD. The median time to follow-up in those surviving TAVR with intraoperative AAD was 1,042 days (range: 648 to 2,666). Surviving patients were managed through thoracic endovascular aortic repair and medical management. In conclusion, in this highly selected cohort of patients, our experience indicates that AAD after TAVR is a rare but often lethal intraprocedural sequela of THV implantation, especially in cases of type A aortic dissection.

A Severe and Fatal Type A Aortic Dissection in an Adult with a Repaired Tetralogy of Fallot.

We report a case of a 44-year-old woman surgically treated for tetralogy of Fallot who experienced an acute and extensive Stanford A type aortic dissection despite the meticulous follow-up. While aortic dilatation is prevalent in individuals with repaired tetralogy of Fallot, aortic dissection represents a rare consequence, that when it appears, is progressive and usually detected during the check-up visits. In the case reported, the dissection was unexpected and severe, and the patient's clinical state worsened suddenly, leading to death after a few days. Constant awareness for aortic aneurysms is essential in the Fallot tetralogy population, nevertheless, several causes may contribute to the acute worsening of the clinical condition until the patient's death.

[Retrograde Stanford Type A Aortic Dissection of Marfan Syndrome Long After Thoracic Endovascular Aortic Repair:Report of a Case].

A 52-year-old woman with Marfan syndrome developed Stanford type B aortic dissection and was treated with thoracic endovascular aortic repair. However, 29 months later, she presented with retrograde Stanford type A aortic dissection. We successfully performed aortic arch replacement with the frozen elephant trunk technique and valve-sparing aortic root replacement. The advantages of the frozen elephant trunk technique are that the distal anastomosis can be created without stent-graft resection and the cardiac arrest time is shortened. Therefore, the frozen elephant trunk technique was considered valuable and safe in this potentially lethal situation.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Causal relationship between type 2 diabetes mellitus and aortic dissection: insights from two-sample Mendelian randomization and mediation analysis.

Objective: Some evidence suggests a reduced prevalence of type 2 diabetes mellitus (T2DM) in patients with aortic dissection (AD), a catastrophic cardiovascular illness, compared to general population. However, the conclusions were inconsistent, and the causal relationship between T2DM and AD remains unclear. Methods: In this study, we aimed to explore the causal relationship between T2DM and AD using bidirectional Mendelian randomization (MR) analysis. Mediation MR analysis was conducted to explore and quantify the possible mediation effects of 1400 metabolites in T2DM and AD. Results: The results of 26 datasets showed no causal relationship between T2DM and AD (P>0.05). Only one dataset (ebi-a-GCST90006934) showed that T2DM was a protective factor for AD (I9-AORTDIS) (OR=0.815, 95%CI: 0.692-0.960, P=0.014), and did not show horizontal pleiotropy (P=0.808) and heterogeneity (P=0.525). Vanillic acid glycine plays a mediator in the causal relationship between T2DM and AD. The mediator effect for vanillic acid glycine levels was -0.023 (95%CI: -0.066-0.021). Conclusion: From the perspective of MR analysis, there might not be a causal relationship between T2DM and AD, and T2DM might not be a protective factor for AD. If a causal relationship does exist between T2DM and AD, with T2DM serving as a protective factor, vanillic acid glycine may act as a mediator and enhance such a protective effect.

Delayed acute myocardial infarction in a young man with traumatic multivessel coronary artery dissection after blunt chest injury.

A man in his 20s with no medical illness sustained a blunt chest injury with pneumothorax and lung contusion after involving in a motorbike accident. Five days postadmission, he subsequently had myocardial infarction with cardiac arrest, in which coronary angiogram and intravascular ultrasound showed diffused multivessel coronary artery dissection.