A cell atlas of thoracic aortic perivascular adipose tissue: a focus on mechanotransducers.

Perivascular adipose tissue (PVAT) is increasingly recognized for its function in mechanotransduction. However, major gaps remain in our understanding of the cells present in PVAT, as well as how different cells contribute to mechanotransduction. We hypothesized that snRNA-seq would reveal the expression of mechanotransducers, and test one (PIEZO1) to illustrate the expression and functional agreement between single-nuclei RNA sequencing (snRNA-seq) and physiological measurements. To contrast two brown tissues, subscapular brown adipose tissue (BAT) was also examined. We used snRNA-seq of the thoracic aorta PVAT (taPVAT) and BAT from male Dahl salt-sensitive (Dahl SS) rats to investigate cell-specific expression mechanotransducers. Localization and function of the mechanostransducer PIEZO1 were further examined using immunohistochemistry (IHC) and RNAscope, as well as pharmacological antagonism. Approximately 30,000 nuclei from taPVAT and BAT each were characterized by snRNA-seq, identifying eight major cell types expected and one unexpected (nuclei with oligodendrocyte marker genes). Cell-specific differential gene expression analysis between taPVAT and BAT identified up to 511 genes (adipocytes) with many (≥20%) being unique to individual cell types. Piezo1 was the most highly, widely expressed mechanotransducer. The presence of PIEZO1 in the PVAT but not the adventitia was confirmed by RNAscope and IHC in male and female rats. Importantly, antagonism of PIEZO1 by GsMTX4 impaired the PVAT's ability to hold tension. Collectively, the cell compositions of taPVAT and BAT are highly similar, and PIEZO1 is likely a mechanotransducer in taPVAT.NEW & NOTEWORTHY This study describes the atlas of cells in the thoracic aorta perivascular adipose tissue (taPVAT) of the Dahl-SS rat, an important hypertension model. We show that mechanotransducers are widely expressed in these cells. Moreover, PIEZO1 expression is shown to be restricted to the taPVAT and is functionally implicated in stress relaxation. These data will serve as the foundation for future studies investigating the role of taPVAT in this model of hypertensive disease.

Coral reef aorta: a rare form of obstruction of the ascending aorta in adolescent with aortopathy- case report.

BACKGROUND: Supra aortic obstruction in children is uncommon and is seen in certain unique conditions. While intraluminal obstruction due to heavy calcification is seen in older populations, it is not described in pediatric populations. The coral reef aorta is a rare and distinct calcifying disease causing luminal obstruction of the suprarenal aorta in adults. The definition of this diagnosis relies entirely on the unique aspects and consistency of the lesions, which are rock-hard, irregular, gritty plaques with a white luminal surface resembling a coral reef. However, no such case has been described in children. CASE PRESENTATION: We present an adolescent boy who presented with a heavily calcified ascending aortic lesion associated with aortopathy and hypertension, 12 years after an aortic coarctation repair. The investigations included echocardiography, magnetic resonance and computer-tomographic imaging. A 3-D model was printed in order to visualize and plan surgical steps in advance for safe placement of clamps and defining the extent of resection. In addition, it provided an idea about tissue quality, thickness, spatial relationship, and orientation in relation to surrounding structures. Successful resection and replacement of the diseased segment of the aorta were achieved on cardiopulmonary bypass support. Post-operative recovery was uneventful, and at 6-month follow-up, the patient is doing well. In this report, various aspects of such lesions have been discussed, including clinical presentations, complications, planning and conduct of a safe cardiopulmonary bypass, and precautions during surgery for a successful outcome. CONCLUSION: Complicated obstructive aortic lesions in children require careful assessment, appropriate advanced imaging, and the use of 3-D printing technology in order to plan and perform safe and effective surgical management. The etiology of severe calcified aorta in children may be related to metabolic factors, previous surgery, use of a homograft, or an inflammatory process. However, it has yet to be proven.

Aortic calcification correlates with pseudoaneurysm or penetrating aortic ulcer of different etiologies.

Chronic risk factors for pseudoaneurysm (PSA) or penetrating aortic ulcer (PAU) have not been fully clarified. This study aims to evaluate the association of aortic calcification with PSA or PAU of different etiologies. Totally 77 pseudoaneurysms, 80 PAU, and 160 healthy controls (HCs) were retrospectively included, of which 30 were infected, 34 were immunological, and 93 were atherosclerotic etiologies. The aortic calcification status, position of aortic tears/ulcers, and risk factors for disease or acute aortic syndrome (AAS) were identified. Atherosclerotic patients aged more than 65 and infective patients aged more than 60 had significantly higher calcification scores. The immunological group had a lower level of calcification in the infrarenal aorta. For patients of infective or atherosclerotic etiology, 60% (18/30) and 60.22% (56/93) of the tears/ulcers occurred at the aortic parts with the highest level of calcification. Patients with longitudinal calcification exceeding 1/3 of the aortic arch had an increased risk of acquiring diseases (OR = 13.231). The presence of longitudinal calcification of the descending aorta or cross-sectional calcification of the infrarenal aorta increased the risks of acquiring diseases (OR = 8.484 and 8.804). After adjusting for age, longitudinal calcification of the descending aorta exceeding 1/3 length was found to be associated with AAS (OR = 4.662). Tears/ulcers of pseudoaneurysm and PAU were both generally found at the part of the aorta with most calcification. Distinct aorta calcification characteristics were observed for lesions of different etiologies. Longitudinal thoracic and cross-sectional infrarenal abdominal aortic calcification increased the risk of acquiring diseases, and descending aortic calcification was associated with symptomatic patients.

Management of esophageal cancer in patients with a right aortic arch or double aortic arch: a case series of 34 cases.

BACKGROUND: Few cases describing patients with a right aortic arch (RAA) or double aortic arch (DAA) and esophageal cancer (EC) have been reported. METHODS: We analyzed RAA and DAA cases treated with esophagectomy in our center's database and reported in English-language studies until April 1, 2023. Our study assessed the malformation characteristics and surgical details of EC patients with RAA and DAA. RESULTS: We extracted data of 24 EC patients with RAAs and 10 EC patients with DAAs. In both groups, the patients were more likely to be Japanese and male, to have squamous cell carcinoma and to have tumors located in the upper thoracic esophagus or middle thoracic esophagus. Left thoracotomy was commonly applied for RAA patients. For DAA patients, the proportions of left-sided and right-sided approaches were similar. Esophagectomy under video-assisted thoracoscopic surgery (VATS) in RAA or DAA patients had been performed on a routine basis in recent years. There were two anastomotic leakages in each group. Specifically, Kommerell diverticulum rupture occurred in 1 RAA patient; gastric tube dilation occurred in 1 DAA patient; and recurrent laryngeal nerve (RLN) injury occurred in 2 RAA patients. The postoperative course was uneventful for most patients in both cohorts. CONCLUSIONS: Esophageal carcinoma is rarely seen in patients with an RAA or DAA. To adequately dissect superior mediastinal LNs, an auxiliary incision (such as sternotomy), the left door open method or a preceding cervical procedure should be used appropriately. Esophagectomy, whether via thoracotomy or thoracoscopic surgery, can be performed safely for both RAA and DAA.

Multiscale insights into postnatal aortic development.

Despite its vital importance for establishing proper cardiovascular function, the process through which the vasculature develops and matures postnatally remains poorly understood. From a clinical perspective, an ability to mechanistically model the developmental time course in arteries and veins, as well as to predict how various pathologies and therapeutic interventions alter the affected vessels, promises to improve treatment strategies and long-term clinical outcomes, particularly in pediatric patients suffering from congenital heart defects. In the present study, we conducted a multiscale investigation into the postnatal development of the murine thoracic aorta, examining key allometric relations as well as relationships between in vivo mechanical stresses, collagen and elastin expression, and the gradual accumulation of load-bearing constituents within the aortic wall. Our findings suggest that the production of fibrillar collagens in the developing aorta associates strongly with the ratio of circumferential stresses between systole and diastole, hence emphasizing the importance of a pulsatile mechanobiological stimulus. Moreover, rates of collagen turnover and elastic fiber compaction can be inferred directly by synthesizing transcriptional data and quantitative histological measurements of evolving collagen and elastin content. Consistent with previous studies, we also observed that wall shear stresses acting on the aorta are similar at birth and in maturity, supporting the hypothesis that at least some stress targets are established early in development and maintained thereafter, thus providing a possible homeostatic basis to guide future experiments and inform future predictive modeling.

Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. METHODS: We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. RESULTS: Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. CONCLUSIONS: Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.

Multi-Omics of Familial Thoracic Aortic Aneurysm and Dissection: Calcium Transport Impairment Predisposes Aortas to Dissection.

Several genetic defects, including a mutation in myosin heavy chain 11 (Myh11), are reported to cause familial thoracic aortic aneurysm and dissection (FTAAD). We recently showed that mice lacking K1256 of Myh11 developed aortic dissection when stimulated with angiotensin II, despite the absence of major pathological phenotypic abnormalities prior to stimulation. In this study, we used a comprehensive, data-driven, unbiased, multi-omics approach to find underlying changes in transcription and metabolism that predispose the aorta to dissection in mice harboring the Myh11 K1256del mutation. Pathway analysis of transcriptomes showed that genes involved in membrane transport were downregulated in homozygous mutant (Myh11ΔK/ΔK) aortas. Furthermore, expanding the analysis with metabolomics showed that two mechanisms that raise the cytosolic Ca2+ concentration-multiple calcium channel expression and ADP-ribose synthesis-were attenuated in Myh11ΔK/ΔK aortas. We suggest that the impairment of the Ca2+ influx attenuates aortic contraction and that suboptimal contraction predisposes the aorta to dissection.

COVID-19-related Floating Thrombus in the Ascending Aorta - A Case Report.

BACKGROUND/AIM: Multiple aortic mural thrombi at the level of the ascending aorta represent a rare condition, only isolated cases have been reported so far. The aim of the current article was to report the case of a 61-year-old patient diagnosed with this pathology. CASE REPORT: A 61-year-old patient with history of COVID infection six months previously was initially diagnosed with acute upper right limb ischemia and submitted to Fogarty desobstruction. Furthermore, the patient was diagnosed with a free-floating mass in the ascending aorta, for which he was submitted to aortotomy and floating thrombi, measuring 5.6×1.5 cm and 3×1.5 cm, were completely removed. The postoperative outcomes were favorable; at the three month follow up the patient proved to have a perfect circulated aortic lumen and supra-aortic vessels. CONCLUSION: immediate aortic desobstruction followed by reconstruction might be a lifesaving maneuver in ascending aortic thrombosis.

Intrinsic histological and morphological abnormalities of the pediatric thoracic aorta in bicuspid aortic valve patients are predictive for future aortopathy.

BACKGROUND: Patients with a bicuspid aortic valve (BAV) have an increased risk to develop aortic complications. Many studies are pointing towards a possible embryonic explanation for the development of both a bicuspid aortic valve as well as a defective ascending aortic wall in these patients. The fetal and newborn ascending aortic wall has however scarcely been studied in bicuspid aortic valve patients. We hypothesize that early histopathological defects might already be visible in the fetal and pediatric ascending aortic wall of bicuspid aortic valve patients, indicating at an early embryonic defect. METHODS: Non-dilated BAV ascending aortic wall samples were collected (n = 40), categorized in five age groups: premature (age range 17.5 weeks + days GA till 37.6 weeks + days GA) 2. neonate (age range 1 - 21 days) 3. infant (age range 1 month - 4 years) 4. adolescent (age range 12 years - 15 years) and 5. adult (age range 41 - 72 years). Specimen were studied for intimal and medial histopathological features. RESULTS: The premature ascending aortic wall has a significantly thicker intimal and significantly thinner medial layer as compared to all other age categories (p < 0.05). After birth the intimal thickness decreases significantly. The medial layer increases in thickness before adulthood (p < 0.05) with an increasing number of elastic lamellae (p < 0.01) and interlamellar mucoid extracellular matrix accumulation (p < 0.0001). Intimal atherosclerosis was scarce and medial histopathological features such as overall medial degeneration, smooth muscle cell nuclei loss and elastic fiber fragmentation were not appreciated in the BAV ascending aortic wall of any age. CONCLUSIONS: The main characteristics of a bicuspid ascending aortic wall are already present before adulthood, albeit not before birth. Considering the early manifestations of ascending aortic wall pathology in bicuspid aortic valve patients, the pediatric population should be considered while searching for markers predictive for future aortopathy.

Evaluation of the therapeutic effects of oestradiol on the systemic inflammatory response and on lung injury caused by the occlusion of the proximal descending aorta in male rats.

OBJECTIVES: Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17ß-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17ß-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. METHODS: Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17ß-oestradiol (280 µg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1ß, IL-10 and tumour necrosis factor-α were quantified. RESULTS: After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17ß-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17ß-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1ß increased after I/R and 17ß-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1ß and IL-10 in lung explants, reduced by 17ß-oestradiol. CONCLUSIONS: Our results showed that 17ß-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17ß-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.

ECG-gated MR angiography at 3T for follow-up after surgery involving the ascending aorta.

We aimed to evaluate electrocardiogram (ECG)-gated MR angiography (MRA) in the follow-up after surgery involving the ascending aorta regarding technical feasibility, image quality, spectrum of findings, and their implications for clinical management. We retrospectively analyzed a cohort of 19 patients (median age 59 years, range 38-79 years), who underwent MRA for follow-up imaging after surgery involving the ascending aorta. Our magnetic resonance imaging protocol consisted of a time-resolved, non-ECG-gated MRA and an ECG-gated MRA performed at 3T. Median examination duration was 25 minutes (range 11-41 minutes). All examinations were assessed by 2 readers in consensus for image quality on a 5-point scale ranging from 1 (non-diagnostic) to 5 (excellent). MRA examinations and patient charts were analyzed for diagnostic findings and their consequences for further management. Subjective image quality was rated as "sufficient" (score 3.1 ±â€…1.1) for the aortic root and as "good" to "excellent" for the ascending aorta (score 4.5 ±â€…0.7), aortic arch (4.5 ±â€…0.7), supra-aortic branches (4.5 ±â€…0.6) and descending aorta (4.6 ±â€…0.7). Abnormal findings were seen in 6 patients (32%) including progressive diameter of remaining aneurysm or dissection (3 patients, 16%) and suture aneurysms (3 patients, 16%). In all 6 of these patients, abnormal findings at MRA had consequences for clinical management. ECG-gated MR angiography at 3T yields good image quality for post-operative surveillance after aortic surgery involving the ascending aorta. This technique may serve as an alternative to computed tomography particularly in younger patients with repeated follow-up.

Natural history of aortic root dilatation and pathologic aortic regurgitation in tetralogy of Fallot and its morphological variants.

OBJECTIVE: We sought to characterize the natural history of aortic root dilatation and aortic regurgitation in tetralogy of Fallot (TOF). METHODS: A single-center review of patients who underwent TOF repair from January 1960 to December 2022 was performed. Morphology was categorized as TOF-pulmonary stenosis or TOF-variant (including TOF-pulmonary atresia and TOF-pulmonary atresia-major aortopulmonary collateral arteries). Echocardiographically determined diameters and derived z scores were measured at the annulus, sinus of Valsalva, and sinotubular junction immediately before TOF repair and throughout follow-up. Linear mixed-effects models assessed trends in dimensions over time. RESULTS: Of 2205 patients who underwent primary repair of TOF at a median age of 4.9 months (interquartile range, 2.3-20.5 months) and survived to discharge, 1608 (72.9%) patients had TOF-pulmonary stenosis and 597 (27.1%) patients had TOF-variant. At a median postoperative follow-up of 14.4 years (interquartile range, 3.3-27.6 years; range, 0.1-62.6 years), 313 (14.2%) patients had mild or greater aortic regurgitation and 34 (1.5%) patients required an aortic valve or root intervention. The overall mean rates of annular, sinus of Valsalva, and sinotubular junction growth were 0.5 ± 0.2, 0.6 ± 0.3, and 0.7 ± 0.5 mm/year, respectively. Root z scores remained stable with time. At baseline, patients with TOF-variant had larger diameters and z scores at the annulus, sinus of Valsalva, and sinotubular junction, compared with patients with TOF-pulmonary stenosis (all P values < .05). Over time, patients with TOF-variant demonstrated relatively greater annular (P = .020), sinus of Valsalva (P < .001), and sinotubular junction (P < .001) dilatation. Patients with ≥75th percentile root growth rates had a higher incidence of mild or greater aortic regurgitation (P < .001), moderate or greater aortic regurgitation (P < .001), and aortic valve repair or replacement (P = .045). CONCLUSIONS: Patients with TOF-variant are at comparatively greater risk of pathologic root dilatation over time, warranting closer longitudinal follow-up.

[Latest Findings on the Pathogenic Mechanisms of Thoracic Aortic Dissection].

Thoracic aortic dissection (TAD) is a cardiovascular disease entailing a high lethality between 65% and 85%. Surgery-assissed implant/interventional stenting is the prevailing treatment of TAD. However, surgical treatment can cause severe postoperative complications and patients incur a relatively higher risk of postoperative mortality. Since the pathogenic mechanism underlying TAD is not clear, effective medication therapies are still not available. In recent years, along with advances in single-cell sequencing and other molecular biological technologies, there have been prelimiary findings suggesting the special role of dysfunctional vascular smooth muscle cells (VSMCs) in the pathogenesis and development of TAD. Furthermore, the molecular mechanisms regulating the dysfunction of VSMCs have been initially explored. It is expected that these new findings will contribute to the development of new strategies to prevent TAD and lead to new ideas for the identifiction of potential drug therapeutic targets. Herein, we summarized the critical role of dysfunctional VSMCs in the pathogenesis and development of TAD and presented in detail the biological factors and the related molecular mechanisms that regulate the dysfunction of VSMCs. We hope this review will provide a reference for further investigation into the central role of dysfunctional VSMCs in the pathogenesis and development of TAD and exploration for effective molecular drug targets for TAD.

Transpericardial resection of a mediastinal paraganglioma.

Paragangliomas are tumours originating from the autonomic nervous system and rarely occur in the chest. They may manifest through symptoms of excess catecholamine release or due to local compression, can be an incidental finding on a computed tomography/magnetic resonance imaging examination or can be found when screening patients with specific gene mutations. Surgical removal is indicated in case of symptoms, (imminent) compression of vital structures or to prevent progression to malignancy. Resection of a paraganglioma in the middle mediastinum can be challenging. The relationship of the tumour to vital structures and its blood supply determine the surgical access route. In this case report, a large paraganglioma situated in the middle mediastinum is resected. Because of the close relationship to vital structures and the presence of feeding arteries from the aortic arch, a transsternal transpericardial approach is chosen. After a median sternotomy, stepwise dissection between the aorta, superior caval vein and right pulmonary artery and the opening of the posterior pericardium gives access to the middle mediastinum and the area between the tracheal bifurcation and the left atrial roof. These steps can be done without cardiopulmonary bypass. After identification and division of the feeding aortic arch arteries, the highly vascularized tumour can be further dissected and removed.

Capacity for LDL (Low-Density Lipoprotein) Retention Predicts the Course of Atherogenesis in the Murine Aortic Arch.

BACKGROUND: To cause atherosclerosis, LDLs (low-density lipoproteins) must first pass through the endothelium and then become retained in the arterial matrix. Which of these two processes is rate-limiting and predicts the topography of plaque formation remains controversial. To investigate this issue, we performed high-resolution mapping of LDL entry and retention in murine aortic arches before and during atherosclerosis development. METHODS: Maps of LDL entry and retention were created by injecting fluorescently labeled LDL followed by near-infrared scanning and whole-mount confocal microscopy after 1 hour (entry) and 18 hours (retention). By comparing arches between normal mice and mice with short-term hypercholesterolemia, we analyzed changes in LDL entry and retention during the LDL accumulation phase that precedes plaque formation. Experiments were designed to secure equal plasma clearance of labeled LDL in both conditions. RESULTS: We found that LDL retention is the overall limiting factor for LDL accumulation but that the capacity for LDL retention varied substantially over surprisingly short distances. The inner curvature region, previously considered a homogenous atherosclerosis-prone region, consisted of dorsal and ventral zones with high capacity and a central zone with low capacity for continued LDL retention. These features predicted the temporal pattern of atherosclerosis, which first appeared in the border zones and later in the central zone. The limit to LDL retention in the central zone was intrinsic to the arterial wall, possibly caused by saturation of the binding mechanism, and was lost upon conversion to atherosclerotic lesions. CONCLUSIONS: Capacity for continued LDL retention varies over short distances and predicts where and when atherosclerosis develops in the mouse aortic arch.

Global and local stiffening of ex vivo-perfused stented human thoracic aortas: A mock circulation study.

The effects of thoracic endovascular repair (TEVAR) on the biomechanical properties of aortic tissue have not been adequately studied. Understanding these features is important for the management of endograft-triggered complications of a biomechanical nature. This study aims to examine how stent-graft implantation affects the elastomechanical behavior of the aorta. Non-pathological human thoracic aortas (n=10) were subjected to long-standing perfusion (8h) within a mock circulation loop under physiological conditions. To quantify compliance and its mismatch in the test periods without and with a stent, the aortic pressure and the proximal cyclic circumferential displacement were measured. After perfusion, biaxial tension tests (stress-stretch) were carried out to examine the stiffness profiles between non-stented and stented tissue, followed by a histological assessment. Experimental evidence shows: (i) a significant reduction in aortic distensibility after TEVAR, indicating aortic stiffening and compliance mismatch, (ii) a stiffer behavior of the stented samples compared to the non-stented samples with an earlier entry into the nonlinear part of the stress-stretch curve and (iii) strut-induced histological remodeling of the aortic wall. The biomechanical and histological comparison of the non-stented and stented aortas provides new insights into the interaction between the stent-graft and the aortic wall. The knowledge gained could refine the stent-graft design to minimize the stent-induced impacts on the aortic wall and the resulting complications. STATEMENT OF SIGNIFICANCE: Stent-related cardiovascular complications occur the moment the stent-graft expands on the human aortic wall. Clinicians base their diagnosis on the anatomical morphology of CT scans while neglecting the endograft-triggered biomechanical events that compromise aortic compliance and wall mechanotransduction. Experimental replication of endovascular repair in cadaver aortas within a mock circulation loop may have a catalytic effect on biomechanical and histological findings without an ethical barrier. Demonstrating interactions between the stent and the wall can help clinicians make a broader diagnosis such as ECG-triggered oversizing and stent-graft characteristics based on patient-specific anatomical location and age. In addition, the results can be used to optimize towards more aortophilic stent grafts.

ADAMTS-7 deficiency attenuates thoracic aortic aneurysm and dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening cardiovascular disease with severe extracellular matrix (ECM) remodeling that lacks efficient early stage diagnosis and nonsurgical therapy. A disintegrin and metalloproteinase with thrombospondin motif 7 (ADAMTS-7) is recognized as a novel locus for human coronary artery atherosclerosis. Previous work by us and others showed that ADAMTS-7 promoted atherosclerosis, postinjury neointima formation, and vascular calcification. However, whether ADAMTS-7 is involved in TAAD pathogenesis is unknown. We aimed to explore the alterations in ADAMTS-7 expression in human and mouse TAAD, and investigate the role of ADAMTS-7 in TAAD formation. A case-control study of TAAD patients (N = 86) and healthy participants (N = 88) was performed. The plasma ADAMTS-7 levels were markedly increased in TAAD patients within 24 h and peaked in 7 days. A TAAD mouse model was induced with 0.5% ß-aminopropionitrile (BAPN) in drinking water. ELISA analysis of mouse plasma, Western blotting, and immunohistochemical staining of aorta showed an increase in ADAMTS-7 in the early stage of TAAD. Moreover, ADAMTS-7-deficient mice exhibited significantly attenuated TAAD formation and TAAD rupture-related mortality in both male and female mice, which was accompanied by reduced artery dilation and inhibited elastin degradation. ADAMTS-7 deficiency caused repressed inflammatory response and complement system activation during TAAD formation. An increase in plasma ADAMTS-7 is a novel biomarker for human TAAD. ADAMTS-7 deficiency attenuates BAPN-induced murine TAAD. ADAMTS-7 is a potential novel target for TAAD diagnosis and therapy. KEY MESSAGES: A case-control study revealed increased plasma ADAMTS-7 is a risk factor for TAAD. ADAMTS-7 was elevated in plasma and aorta at early stage of mouse TAAD. ADAMTS-7 knockout attenuated mouse TAAD formation and mortality in both sexes.

Predicting the Risk of Type B Aortic Dissection Using Hemodynamic Parameters in Aortic Arches: A Comparative Study between Healthy and Repaired Aortas.

BACKGROUND AND OBJECTIVE: The development of acute aortic dissection (AD) remains unpredictable due to the intricate nature of the AD mechanism and the varied patient-specific aortic anatomy. The aim of this study was to simulate the hemodynamic parameters in the aortas before the onset of TBAD with healthy controls. METHODS: This study numerically assessed the effectiveness of hemodynamic indicators in predicting the risk of type B AD (TBAD) by investigating the differences in hemodynamic parameters between healthy and repaired aortas (aortas before TBAD development). Four wall shear stress (WSS)-based indicators and three helicity-based indicators were adopted and analyzed. RESULTS: The results showed that more pathological anatomical feathers can be observed in the repaired aortas. For WSS-based indicators, only averaged cross flow index (CFI) and oscillatory shear index OSI (CFI, 1.03 ± 0.07 vs. 0.83 ± 0.10 and OSI, 0.12 ± 0.03 vs. 0.04 ± 0.02) (all p<0.001) were significantly higher in the repaired aortas than those in the healthy aortas. On the other hand, average helicity in the repaired aortas also showed a significant difference compared with that in healthy aortas (h1, 3.88 ± 5.55 vs. -8.03 ± 14.16) (p<0.05). Furthermore, the skewed helical structure and flow disturbance was found in the repaired aortas. CONCLUSION: 1) There are marked differences in pathological anatomical features, such as aortic dilation, elongation and tortuosity between the healthy aortas and repaired aortas, and the corresponding hemodynamic indicators also have also been significantly changed. 2) Compared with anatomical characteristics, hemodynamic indicators may be more accurate for predicting the risk and location of TBAD, such as the OSI and CFI index were significantly enhanced in the region where the entry tears have occurred. 3) In clinical practice, anatomical features remain important factors for assessing the risk for development of TBAD; however, hemodynamic analyses with quantitative data and more visualizing characteristics have showed promising potential in this aspect.

Predictors of the difficulty of transcervical subcarinal lymph node dissection for esophageal cancer.

BACKGROUND: Transmediastinal radical esophagectomy (TME) is a new minimally invasive approach without thoracotomy. However, the transcervical dissection of subcarinal lymph nodes (SCLN) is challenging. The shape or narrowness of the mediastinal space, particularly around the aortic arch to the tracheal bifurcation, may increase the difficulty of this procedure. The present study aimed to clarify predictors of the difficulty of transcervical SCLN dissection. METHODS: Patients who underwent TME between 2016 and 2019 were included (n = 126). Four indicators, the cervical angle, carina distance, aorta distance, and sternum distance, were defined as indicators of mediastinal narrowness by 3D-CT. The relationships between the difficulty of transcervical SCLN dissection and clinicopathological features, including the above indicators, were investigated. RESULTS: In a univariate analysis, the cervical angle (p = 0.023), aorta distance (p = 0.002), and middle thoracic tumor (p = 0.040) correlated with difficulty. The median cervical angle and aorta distance were 15° and 33 mm in difficult cases and 19° and 43 mm in easy cases, respectively. In a multivariate analysis, the short aorta distance (odds ratio: 7.96, p = 0.002) and middle thoracic tumor (odds ratio: 3.35, p = 0.042) were independent predictive factors. CONCLUSIONS: The cervical angle, aorta distance, and middle thoracic tumor may predict the difficulty of transcervical SCLN dissection. In difficult cases, a transhiatal approach should be combined for complete SCLN dissection.