Endovascular aortic arch repair with chimney technique for pseudoaneurysm.

BACKGROUND:Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones.METHODS:A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter.RESULTS:The median age of 32 patients was 68.0 years (range, 28-81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred.CONCLUSION:For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.

EphrinB2 promotes the human aortic smooth muscle cell growth and migration via mediating F-actin remodeling.

OBJECTIVES:To evaluate the potential effect of EphrinB2 in human thoracic aortic dissection (TAD) and to illustrate the mechanisms governing the role of EphrinB2 in the growth of human aortic smooth muscle cells (HASMC).METHODS:In the study, EphrinB2 expression was investigated by qRT-PCR and immunohistochemistry in 12 pairs of TAD and adjacent human tissues. HASMCs were used for in vitro experiments. Next, EphrinB2 overexpression and depletion in HASMCs were established by EphrinB2-overexpressing vectors and small interfering RNA, respectively. The transfection efficiency was evaluated by qRT-PCR and Western blot. The effects of overexpression and depletion of EphrinB2 on cell proliferation, migration, and invasion were tested in vitro. Cell Counting Kit-8, flow cytometry and transwell migration/invasion, and wound healing assay were used to explore the function of EphrinB2 on HASMC cell lines. The relationship between EphrinB2 and F-actin was assessed by Western blot, immunofluorescence, and Co-IP.RESULTS:We found that EphrinB2 was a prognostic biomarker of TAD patients. Moreover, EphrinB2 expression negatively correlated to aortic dissection tissues, and disease incidence of males, suggesting that EphrinB2 might act as a TAD suppressor by promoting proliferation or decreasing apoptosis in HASMC. Next, over-expression of EphrinB2 in HASMC lines drove cell proliferation, migration, and invasion, and inhibited apoptosis while knockdown EphrinB2 showed the opposite phenomenon, respectively. Furthermore, the level of F-actin in mRNA, protein, and distribution in HASMC cell lines highly matched with the expression of EphrinB2, which indicated that EphrinB2 could mediate the HASMC cytoskeleton via inducing F-actin.CONCLUSIONS:In conclusion, our results first provided the pivotal role of EphrinB2 in HASMC proliferation initiated by mediating F-actin and demonstrated a prognostic biomarker and the potential targets for therapy to prevent thoracic aortic dissection.

Extracellular signal-regulated kinase inhibition prevents venous adaptive remodeling via regulation of Eph-B4.

OBJECTIVES:Vein graft adaptation (VGA) is a process that vein as a vascular graft conduits in arterial reconstructive surgery; VGA can lead to postoperative vein graft stenosis (VGS) and complications after coronary artery bypass graft and other peripheral artery bypass surgeries. VGA is characterized by vein graft loss the venous features without exhibiting arterial features; furthermore, the activation of ERK inhibited the maintenance of venous properties of the vein graft. We hypothesized that ERK inhibition can affect vein VGS through regulating the expression of EphB4.METHODS:Rat vein transplantation model was established using wild-type and EphB4+/- Sprague-Dawley rats. Hematoxylin-eosin, Masson, Verhoeff, actin staining, and immunohistochemistry were applied to observe the structure of the vein grafts. Vascular smooth muscle cells (VSMCs) were isolated from the vein and vein grafts. Western blotting was used to determine the expression of p-ERK1/2 and EphB4, and immunofluorescence was applied to detect the expression and location of EphB4. Cell wound scratch assay and CCK8 assay were used to determine the migration and proliferation of VSMCs. Real-time polymerase chain reaction was used to determine the mRNA expression of EphB4.RESULTS:Western blotting in vein sample and vein graft sample detected p-ERK1/2 and ERK1/2 expression in both EphB4+/+ and EphB4+/- rats. The expression of p-ERK was increased in vein graft compared to vein. Immunofluorescence in VSMCs form EphB4+/+ and EphB4+/- rats detected EphB4 expression in both cells, and the expression of EphB4 was increased in VSMCs form EphB4+/+ rats. SCH772984 reduces the proliferation and migration of VSMCs. Inhibition of ERK suppressed the increase of vein graft wall thickness, and the expression of collagen fibers, elastic fibers, and α-actin was decreased. Vein graft from EphB4+/- rats reduces the expression of EphB4, and SCH772984 suppressed the decrease of EphB4 in vivo. Vein graft from EphB4+/- rats increased the expression of EphB4, and SCH772984 suppressed the increase of EphB4 in vivo.CONCLUSIONS:The inhibition of ERK1/2 suppressed the process of VGS by decreasing the proliferation of VSMCs. The ERK-inhibitor SCH772984 suppressed the level of VGS by extending the time of EphB4 expression during the process of VGA, thus maintaining the venousization of vein graft. The mechanism may be that the inhibitor SCH772984 suppresses the level of VGS by extending the time of EphB4 expression during the process of VGA. Therefore, our research provides a new target of VGS treatment by inhibiting the expression of ERK1/2 through the process of VGA.

Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer.

OBJECTIVES:The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer.METHODS:Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls.RESULTS:The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse.CONCLUSIONS:Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

WITHDRAWN: Endovascular Repair with Stent-Graft of Symptomatic Tuberculous Aortic Pseudoaneurysm

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Midterm Results of Retrograde In Situ Needle Fenestration During Thoracic Endovascular Aortic Repair of Aortic Arch Pathologies.

PURPOSE:To evaluate the safety and feasibility of the in situ needle fenestration (ISNF) technique for reconstruction of the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR) of complicated aortic arch pathologies.MATERIALS AND METHODS:A retrospective review was conducted from January 2014 to December 2019 of 50 patients (mean age 60.2±11.1; 45 men) who underwent ISNF to revascularize the LSA during TEVAR. Twenty-one of the patients also required revascularization of the left common carotid artery (LCCA; n=19) and innominate artery (IA; n=2) using physician-modified in vitro fenestration. Overall, 73 supra-aortic branches were targeted for revascularization.RESULTS:ISNF was successful in 48 patients (96%); one LSA could not be stented and a tortuous LSA prevented the needle from fenestrating the graft. No perioperative major adverse event occurred. There were no type I and 4 type III endoleaks (8%), 3 of which occurred among the first 20 cases. Types II and IV endoleaks were found in 3 (6%) and 6 (12%) cases, respectively; all disappeared during a median follow-up of 15 months (range 3-66). One death (2%) occurred within 12 months due to cerebral hemorrhage. Two patients (4%) required open reinterventions at 6 and 62 months.CONCLUSION:ISNF for revascularization of the LSA during TEVAR seems to be feasible with acceptable midterm outcomes. The learning curve and evolving patient selection criteria affected technical success, complications, and the need for reinterventions. Long-term durability requires further evaluation.

Endovascular Management of a Short-neck Thoracic Aortic Aneurysm With Patent Ductus Arteriosus.

Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset.

Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (as-miR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.

Endovascular aortic arch repair with chimney technique for pseudoaneurysm.

BACKGROUND:Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones.METHODS:A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter.RESULTS:The median age of 32 patients was 68.0 years (range, 28-81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred.CONCLUSION:For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.

EphrinB2 promotes the human aortic smooth muscle cell growth and migration via mediating F-actin remodeling.

OBJECTIVES:To evaluate the potential effect of EphrinB2 in human thoracic aortic dissection (TAD) and to illustrate the mechanisms governing the role of EphrinB2 in the growth of human aortic smooth muscle cells (HASMC).METHODS:In the study, EphrinB2 expression was investigated by qRT-PCR and immunohistochemistry in 12 pairs of TAD and adjacent human tissues. HASMCs were used for in vitro experiments. Next, EphrinB2 overexpression and depletion in HASMCs were established by EphrinB2-overexpressing vectors and small interfering RNA, respectively. The transfection efficiency was evaluated by qRT-PCR and Western blot. The effects of overexpression and depletion of EphrinB2 on cell proliferation, migration, and invasion were tested in vitro. Cell Counting Kit-8, flow cytometry and transwell migration/invasion, and wound healing assay were used to explore the function of EphrinB2 on HASMC cell lines. The relationship between EphrinB2 and F-actin was assessed by Western blot, immunofluorescence, and Co-IP.RESULTS:We found that EphrinB2 was a prognostic biomarker of TAD patients. Moreover, EphrinB2 expression negatively correlated to aortic dissection tissues, and disease incidence of males, suggesting that EphrinB2 might act as a TAD suppressor by promoting proliferation or decreasing apoptosis in HASMC. Next, over-expression of EphrinB2 in HASMC lines drove cell proliferation, migration, and invasion, and inhibited apoptosis while knockdown EphrinB2 showed the opposite phenomenon, respectively. Furthermore, the level of F-actin in mRNA, protein, and distribution in HASMC cell lines highly matched with the expression of EphrinB2, which indicated that EphrinB2 could mediate the HASMC cytoskeleton via inducing F-actin.CONCLUSIONS:In conclusion, our results first provided the pivotal role of EphrinB2 in HASMC proliferation initiated by mediating F-actin and demonstrated a prognostic biomarker and the potential targets for therapy to prevent thoracic aortic dissection.

Extracellular signal-regulated kinase inhibition prevents venous adaptive remodeling via regulation of Eph-B4.

OBJECTIVES:Vein graft adaptation (VGA) is a process that vein as a vascular graft conduits in arterial reconstructive surgery; VGA can lead to postoperative vein graft stenosis (VGS) and complications after coronary artery bypass graft and other peripheral artery bypass surgeries. VGA is characterized by vein graft loss the venous features without exhibiting arterial features; furthermore, the activation of ERK inhibited the maintenance of venous properties of the vein graft. We hypothesized that ERK inhibition can affect vein VGS through regulating the expression of EphB4.METHODS:Rat vein transplantation model was established using wild-type and EphB4+/- Sprague-Dawley rats. Hematoxylin-eosin, Masson, Verhoeff, actin staining, and immunohistochemistry were applied to observe the structure of the vein grafts. Vascular smooth muscle cells (VSMCs) were isolated from the vein and vein grafts. Western blotting was used to determine the expression of p-ERK1/2 and EphB4, and immunofluorescence was applied to detect the expression and location of EphB4. Cell wound scratch assay and CCK8 assay were used to determine the migration and proliferation of VSMCs. Real-time polymerase chain reaction was used to determine the mRNA expression of EphB4.RESULTS:Western blotting in vein sample and vein graft sample detected p-ERK1/2 and ERK1/2 expression in both EphB4+/+ and EphB4+/- rats. The expression of p-ERK was increased in vein graft compared to vein. Immunofluorescence in VSMCs form EphB4+/+ and EphB4+/- rats detected EphB4 expression in both cells, and the expression of EphB4 was increased in VSMCs form EphB4+/+ rats. SCH772984 reduces the proliferation and migration of VSMCs. Inhibition of ERK suppressed the increase of vein graft wall thickness, and the expression of collagen fibers, elastic fibers, and α-actin was decreased. Vein graft from EphB4+/- rats reduces the expression of EphB4, and SCH772984 suppressed the decrease of EphB4 in vivo. Vein graft from EphB4+/- rats increased the expression of EphB4, and SCH772984 suppressed the increase of EphB4 in vivo.CONCLUSIONS:The inhibition of ERK1/2 suppressed the process of VGS by decreasing the proliferation of VSMCs. The ERK-inhibitor SCH772984 suppressed the level of VGS by extending the time of EphB4 expression during the process of VGA, thus maintaining the venousization of vein graft. The mechanism may be that the inhibitor SCH772984 suppresses the level of VGS by extending the time of EphB4 expression during the process of VGA. Therefore, our research provides a new target of VGS treatment by inhibiting the expression of ERK1/2 through the process of VGA.

Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer.

OBJECTIVES:The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer.METHODS:Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls.RESULTS:The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse.CONCLUSIONS:Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

WITHDRAWN: Endovascular Repair with Stent-Graft of Symptomatic Tuberculous Aortic Pseudoaneurysm

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Midterm Results of Retrograde In Situ Needle Fenestration During Thoracic Endovascular Aortic Repair of Aortic Arch Pathologies.

PURPOSE:To evaluate the safety and feasibility of the in situ needle fenestration (ISNF) technique for reconstruction of the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR) of complicated aortic arch pathologies.MATERIALS AND METHODS:A retrospective review was conducted from January 2014 to December 2019 of 50 patients (mean age 60.2±11.1; 45 men) who underwent ISNF to revascularize the LSA during TEVAR. Twenty-one of the patients also required revascularization of the left common carotid artery (LCCA; n=19) and innominate artery (IA; n=2) using physician-modified in vitro fenestration. Overall, 73 supra-aortic branches were targeted for revascularization.RESULTS:ISNF was successful in 48 patients (96%); one LSA could not be stented and a tortuous LSA prevented the needle from fenestrating the graft. No perioperative major adverse event occurred. There were no type I and 4 type III endoleaks (8%), 3 of which occurred among the first 20 cases. Types II and IV endoleaks were found in 3 (6%) and 6 (12%) cases, respectively; all disappeared during a median follow-up of 15 months (range 3-66). One death (2%) occurred within 12 months due to cerebral hemorrhage. Two patients (4%) required open reinterventions at 6 and 62 months.CONCLUSION:ISNF for revascularization of the LSA during TEVAR seems to be feasible with acceptable midterm outcomes. The learning curve and evolving patient selection criteria affected technical success, complications, and the need for reinterventions. Long-term durability requires further evaluation.

Endovascular Management of a Short-neck Thoracic Aortic Aneurysm With Patent Ductus Arteriosus.

Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset.

Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (as-miR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.