Short-Term Disruption of TGFß Signaling in Adult Mice Renders the Aorta Vulnerable to Hypertension-Induced Dissection.

Hypertension and transient increases in blood pressure from extreme exertion are risk factors for aortic dissection in patients with age-related vascular degeneration or inherited connective tissue disorders. Yet, the common experimental model of angiotensin II-induced aortopathy in mice appears independent of high blood pressure as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by co-treatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice 1 week after disruption of TGFß signaling in smooth muscle cells. Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes that was rescued by hydralazine; results were similar with angiotensin II. Changes in regulatory contractile molecule expression were not of pathological significance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically type XVIII, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure cause dissection in aortas rendered vulnerable by inhibition of TGFß-driven extracellular matrix production by smooth muscle cells. A corollary is that medial fibrosis, a frequent feature of medial degeneration, may afford some protection against aortic dissection.

Management of Isolated Abdominal Aortic Dissection: Indications and Strategies for Treatment.

BACKGROUND: The aim of this paper was to report our experience in the management of isolated abdominal aortic dissection with endovascular aortic repair and conservative treatment. METHODS: A cohort of 22 consecutive patients with isolated abdominal aortic dissection was treated between January 2016 and December 2021. We reviewed the demographics, clinical features, therapeutic modalities and follow-up results. Retrospective data analysis from patient charts was performed. RESULTS: Twenty-two patients were enrolled in this study from 2 centers. The mean age was 66.2 ± 13.3 years. Hypertension was the primary risk factor. Seventeen (72.7%) patients were asymptomatic, and 18 patients were subrenal artery type (type II). A total of 12 patients had successful endovascular repair (EVAR), and 10 patients underwent conservative treatment. In the group receiving conservative treatment, no patients required EVAR during follow-up, and 4 patients died. However, none of them had aortic causes: 2 patients had cardiac causes, the other 2 had cancer, and the others remained symptom-free. The latest computed tomographic angiography images showed that abdominal aortic dissection still existed, and the extent of the false lumen did not increase significantly. CONCLUSIONS: Both conservative treatment and EVAR are effective treatment options. Appropriate treatment needs to be performed according to different patients' clinical manifestations and doctors' experience.

Endovascular Repair for Abdominal Aortic Aneurysm in Mainland China: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to evaluate the safety, applicability, and outcomes of the endovascular aneurysm repair (EVAR) technique for patients in mainland China with abdominal aortic aneurysm (AAA) by performing a systematic review. METHODS: We conducted a systematic search using the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to identify Chinese studies on the management of AAAs using the EVAR technique published in English between January 2000 and December 2020. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The included studies investigated the clinical outcomes and postprocedural complications of using EVAR techniques. RESULTS: Sixteen studies reported a total of 3,024 AAA patients. The follow-up period ranged from 1 to 133 months. The mean follow-up time was 38.5 months, the mean age was 69.2 years, and the mean aneurysm diameter was 56.1 mm. The pooled technical success rate was 95% (95% confidence interval [CI]: 92-96%). The endoleak rate was 7% (95% CI: 6-8%). The rate of endoleak requiring reintervention was 3% (95% CI: 3-4%). The 30-day morbidity rate was 9% (95% CI: 6-14%). The 30-day mortality rate was 2% (95% CI: 1-3%). The follow-up mortality was 5% (95% CI: 3-8%). CONCLUSIONS: The results of the study showed that using the EVAR technique for treating patients in mainland China with AAAs produced encouraging mid-term outcomes. Long-term outcomes should be examined in future research.

mTOR inhibition prevents angiotensin II-induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice.

Aortic dissection and rupture are triggered by decreased vascular wall strength and/or increased mechanical loads. We investigated the role of mTOR signaling in aortopathy using a well-described model of angiotensin II-induced dissection, aneurysm, or rupture of the suprarenal abdominal aorta in Apoe-deficient mice. Although not widely appreciated, nonlethal hemorrhagic lesions present as pseudoaneurysms without significant dissection in this model. Angiotensin II-induced aortic tears result in free rupture, contained rupture with subadventitial hematoma (forming pseudoaneurysms), dilatation, or healing, while the media invariably thickens regardless of mural tears. Medial thickening results from smooth muscle cell hypertrophy and extracellular matrix accumulation, including matricellular proteins. Angiotensin II activates mTOR signaling in vascular wall cells, and inhibition of mTOR signaling by rapamycin prevents aortic rupture but promotes dissection. Decreased aortic rupture correlates with decreased inflammation and metalloproteinase expression, whereas extensive dissection correlates with induction of matricellular proteins that modulate adhesion of vascular cells. Thus, mTOR activation in vascular wall cells determines whether aortic tears progress to dissection or rupture. Previous mechanistic studies of aortic aneurysm and dissection by angiotensin II in Apoe-deficient mice should be reinterpreted as clinically relevant to pseudoaneurysms, and mTOR inhibition for aortic disease should be explored with caution.

Mid-term Efficacy and Safety of Drug-coated Balloon versus Nitinol Bare Metal Stent for Primary Lesions in Femoropopliteal Artery Disease.

OBJECTIVES: To compare drug-coated balloon (DCB) and bare metal stent (BMS) for primary lesions in femoropopliteal artery disease in Chinese population and to make subgroup analysis between the groups. METHODS: Patients with primary lesions who underwent BMS or DCB treatment of a single tertiary vascular center were included and followed up for 24 months. Clinical and anatomic status were reported using the criteria recommended by the Society for Vascular Surgery. The primary endpoint included primary patency, clinically target limb revascularization, composite safety endpoint and all-cause death over 24 months assessed by Kaplan-Meier. Secondary endpoints included technical success rate and stent-related complications. RESULTS: A total of 284 patients with 324 limbs were pooled into analysis and most of the baseline characteristics did not show significant difference. A total of 74 in BMS group and 71 in DCB group were claudicants while 83 in BMS group and 56 in DCB group suffered from chronic limb threatening ischemia (CLTI). The mean cumulative lesion length was 18.7 ± 9.8cm in BMS group while 17.2 ± 10.3cm in DCB group. Kaplan-Meier estimates of primary patency were 75.3% and 80.9% for BMS and DCB groups at 12 months while decreased to 63.9% and 70.2% at 24 months (log-rank P = 0.167), respectively. Freedom from clinically driven target limb revascularization was 86.8% and 92.7% for BMS and DCB groups at 12 months while dropped to 82.5% and 85.9% at 24 months (log-rank P = 0.342). Estimates of primary patency between BMS and DCB group did not show significant difference on lesions with poor runoff (58.8% vs. 67.3%, log-rank P = 0.127), severe calcification (64.5% vs. 69.4%, log-rank P = 0.525) and popliteal artery involvement (59.3% vs. 60.3%, log-rank P = 0.695) at 24 months. The overall survival (92.6% for BMS, 90.3% for DCB, log-rank P = 0.391) and freedom from composite safety endpoint (79.3% for BMS, 79.2% for DCB, log-rank P = 0.941) showed no significant difference at 24 months. CONCLUSIONS: Over the 24 month follow-up, BMS and DCB showed equivalent efficacy and safety outcomes for primary femoropopliteal artery disease, which indicated the reduction of permanent metallic implant insertion might be possible.

Excessive adventitial stress drives inflammation-mediated fibrosis in hypertensive aortic remodelling in mice.

Hypertension induces significant aortic remodelling, often adaptive but sometimes not. To identify immuno-mechanical mechanisms responsible for differential remodelling, we studied thoracic aortas from 129S6/SvEvTac and C57BL/6 J mice before and after continuous 14-day angiotensin II infusion, which elevated blood pressure similarly in both strains. Histological and biomechanical assessments of excised vessels were similar at baseline, suggesting a common homeostatic set-point for mean wall stress. Histology further revealed near mechano-adaptive remodelling of the hypertensive 129S6/SvEvTac aortas, but a grossly maladaptive remodelling of C57BL/6 J aortas. Bulk RNA sequencing suggested that increased smooth muscle contractile processes promoted mechano-adaptation of 129S6/SvEvTac aortas while immune processes prevented adaptation of C57BL/6 J aortas. Functional studies confirmed an increased vasoconstrictive capacity of the former while immunohistochemistry demonstrated marked increases in inflammatory cells in the latter. We then used multiple computational biomechanical models to test the hypothesis that excessive adventitial wall stress correlates with inflammatory cell infiltration. These models consistently predicted that increased vasoconstriction against an increased pressure coupled with modest deposition of new matrix thickens the wall appropriately, restoring wall stress towards homeostatic consistent with adaptive remodelling. By contrast, insufficient vasoconstriction permits high wall stresses and exuberant inflammation-driven matrix deposition, especially in the adventitia, reflecting compromised homeostasis and gross maladaptation.

Endovascular In Situ Fenestration Technique of Aortic Arch Pathology: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to evaluate the safety, applicability and outcomes of the endovascular in situ fenestration (ISF) technique for patients with aortic arch pathologies by performing a systematic review. METHODS: We conducted a systematic search using the PubMed, Embase, and Cochrane databases to identify English language articles between January 2004 and March 2019 on the management of aortic arch pathologies using an in situ fenestration technique. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The studies included all investigated the clinical outcomes and postprocedural complications of using ISF techniques. RESULTS: Seven studies reported on a total of 117 aortic arch pathologies patients. Including 52 dissection patients, 47 aneurysm patients, 18 intramural hematomas and penetrating ulcers patients. Needle fenestration and laser fenestration were performed in 62 and 45 patients respectively, and the rest 10 patients received radiofrequency fenestration. The follow-up period ranged from 1 to 55 months. The pooled technical success rates were 94% (95% confidence interval [CI]: 79-98%). The stroke rate was 6% (95% CI: 3-13%). The 30-day MAE was 11% (95% CI: 6-18%). CONCLUSION: The results of the study showed that using the in-situ fenestration technique for treating patients with aortic arch pathologies produced encouraging mid-outcomes. Long-term outcomes remain undefined.

Herbal therapy treatment in thromboangiitis obliterans: a retrospective clinical study.

BACKGROUND: Critical limb ischemia in patients with thromboangiitis obliterans (TAO, Buerger's disease) is associated with refractory rest pain, gangrene, and increased rates of amputation. Tuoju lotion was prepared by the Pharmacy Department of Dongfang Hospital. The focus of the study is to elicit the efficacy of the addition of Herbal therapy treatment to conventional treatment in TAO patients with severe extremity pain and to assess any statistically significant benefits in patient's pain control at rest. We fund that the addition of herbal therapy treatment can augment conventional treatments in TAO patients by improving or eliminating intermittent claudication symptoms, prolonging claudication distance, and reducing total blood viscosity. At the same time, Tuoju lotion can improve microcirculation status in the short term. The purpose of this study was to investigate the effect of topical Herbal therapy treatment on patient outcomes in patients with TAO. METHODS: Seventy patients with TAO treated between January 2009 and July 2019 were included in a retrospective analysis of a single university hospital vascular center. Forty patients received topical herbal treatment in addition to conventional therapy and were compared to a control group who received standard treatment alone (n=30). RESULTS: Patients in both, the experimental and control group, were matched according to age and gender. There was no significant difference in course of disease and past medical history between the two groups. The mean ankle brachial index (ABI), toe pressure, and blood viscosity were also similar in both groups. Rest pain score (baseline VAS 4.76±2.87, post-treatment 3.32±1.29) and walking distance (baseline 169.7±23.6 m, post-treatment 284.5±32.3 m) significantly improved in the herbal treatment group. ABI values improved and total blood viscosity decreased in both groups with no significant difference between the herbal and conservative treatment arms. However, the arterial blood pressure ratio in the lower extremity stage showed no difference between the superficial femoral artery and the popliteal artery. CONCLUSIONS: The addition of Herbal therapy treatment to conventional treatment in TAO patients with severe extremity pain was associated with a reduction of rest pain and intermittent claudication.

Chronic mTOR activation induces a degradative smooth muscle cell phenotype.

Smooth muscle cell (SMC) proliferation has been thought to limit the progression of thoracic aortic aneurysm and dissection (TAAD) because loss of medial cells associates with advanced disease. We investigated effects of SMC proliferation in the aortic media by conditional disruption of Tsc1, which hyperactivates mTOR complex 1. Consequent SMC hyperplasia led to progressive medial degeneration and TAAD. In addition to diminished contractile and synthetic functions, fate-mapped SMCs displayed increased proteolysis, endocytosis, phagocytosis, and lysosomal clearance of extracellular matrix and apoptotic cells. SMCs acquired a limited repertoire of macrophage markers and functions via biogenesis of degradative organelles through an mTOR/ß-catenin/MITF-dependent pathway, but were distinguishable from conventional macrophages by an absence of hematopoietic lineage markers and certain immune effectors even in the context of hyperlipidemia. Similar mTOR activation and induction of a degradative SMC phenotype in a model of mild TAAD due to Fbn1 mutation greatly worsened disease with near-uniform lethality. The finding of increased lysosomal markers in medial SMCs from clinical TAAD specimens with hyperplasia and matrix degradation further supports the concept that proliferation of degradative SMCs within the media causes aortic disease, thus identifying mTOR-dependent phenotypic modulation as a therapeutic target for combating TAAD.

Retroperitoneal Castleman Disease Invading Iliac Vein and Inferior Vena Cava Treated by Tumorectomy with Vascular Repair: A Case Report.

Unicentric Castleman disease, a rare lymphoproliferative disorder, is always known as a solitary, well-defined lymph node enlargement. We reported an extraordinary case of retroperitoneal Castleman disease, which invades wall of right iliac vein and inferior vena cava, treated successfully by tumorectomy with vascular repair.

Engineering of human brain organoids with a functional vascular-like system.

Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.

Rapamycin attenuates a murine model of thoracic aortic aneurysm by downregulating the miR-126-3p mediated activation of MAPK/ERK signalling pathway.

Thoracic aortic aneurysm (TAA) is fatal diseases, which leads to aortic rupture and sudden death. Blood pressure-lowering drugs are ineffective for most of the patients. Our previous study demonstrated the inhibition of endothelial secreted miR-126-3p by rapamycin ameliorate the aneurysmal phenotype of smooth muscle cells (SMCs) in vitro. Hence, this study aimed to evaluate the modulation and mechanism of miR-126-3p in a murine model of TAA (Fbn1C1039G/+). Our results showed that noticeable disturbed flow (DF) was observed in the aorta of Fbn1C1039G/+ mice, and the expression of miR-126-3p was significantly increased under the DF in the cell chamber. This finding was also confirmed by tests in the corresponding DF area of the human aortic aneurysm tissue. Constant rapamycin administration significantly ameliorates the incidence and severity of Fbn1C1039G/+ mice characterized by decreased aortic media degradation, macrophage infiltration and MMP2/9 expression in the aortic wall. Mechanistic studies showed that rapamycin attenuates TAA progression by inhibiting miR-126-3p through ERK1/2 inactivation.

[Endovascular repair of an iliac artery aneurysm after endovascular aneurysm repair with handmade iliac branch device: a case report].

An involved internal iliac artery is usually embolized when performing endovascular aneurysm repair for aortoiliac or isolated iliac artery aneurysm.This can lead to complications such as buttock claudication,colon ischaemia and erectile dysfunction.Iliac branch device (IBD) is an endograft designed specifically for iliac bifurcation to preserve internal iliac flow. It was performed with high technical success rates and encouraging mid-term patency. Here we report a case of right iliac aneurysm developed 3 years after endovascular aneurysm repair for an aortoiliac aneurysm, with the patient's left internal artery been sacrificed then. Using a handmade IBD, we excluded the aneurysm without occlusion of the ipsilateral internal iliac artery or any type of endoleak. Both the design and deployment of this IBD are distinctive that we would like to share our experience with all the colleagues.

[Endovascular treatment of a rare type of aortic arch aneurysm derived from the fourth aortic arch].

OBJECTIVE: To report a rare type of aortic arch aneurysm. METHODS: Three cases of aortic arch aneurysm derived from the fourth aortic arch were retrospectively analyzed. The pathogenesis and treatment of this type of aortic arch aneurysm were investigated. RESULTS: Most of the aneurysm body was located in the Z2 zone, which was the stem from the fourth aortic arch in the embryonic development period. All of the 3 cases could not be explained by common etiology. We speculated that the cause might be developmental anomaly of the fourth aortic arch. All the 3 aortic arch aneurysms were totally excluded with a covered stent. The technical success rate was 100%. Endoleak of type I was seen in one case, which was resolved in a later open surgery. During the follow-up, no type of complications was found. CONCLUSION: To the best of our knowledge, this is the first report of this type of aortic arch aneurysm. The cause may be developmental anomaly of the fourth aortic arch. Endovascular treatment of this type of aortic arch aneurysm is feasible.

New approach to dilation of stenotic lesions through the accessory hepatic vein in Budd-Chiari syndrome.

We investigated a new approach to dilation of stenotic lesions through the femoral vein-accessory hepatic vein-intrahepatic communicating branched vein-hepatic vein-inferior vena cava loop in two cases of Budd-Chiari syndrome. For some selected patients, this approach represents an additional method to increase technical success and to decrease complications.

[Diagnosis and surgical treatment results of angio-Behçet syndrome: an analysis of 26 patients].

OBJECTIVE: To analyze the diagnosis and surgical treatment results of angio-Behçet syndrome. METHODS: The clinical data of pre-operation diagnosis, surgical treatment methods and prospective efficacy of 26 patients who were diagnosed as Behçet syndrome between January 2003 and April 2011 was analyzed retrospectively. There were 23 male and 3 female patients, aging from 20 to 76 years with a mean of (37 ± 6) years. Among them, 3 patients showed the clinical symptoms as arterial stenosis or occlusion, 9 patients had aneurysm, 13 patients had phlebitis or phlebothrombosis. One patient had both aneurysm and venous thrombosis. Totally 11 patients had experienced 22 cases surgical treatment including interventional therapy for 8 cases, open operation for 13 cases and hybrid operation for 1 case. RESULTS: Twenty-two patients (84.6%) were followed up from 3 months to 96 months after various surgical treatment methods. The average follow-up periond was 39.3 months. Totally, perioperative mortality was 1/11 after surgical treatment. Healing rates were 7/8 and 8/13, recurrence rates were 5/8 and 7/8 in patients with interventional therapy compared with that of experiencing open surgery respectively. CONCLUSIONS: Behçet syndrome patients combined with various vascular lesions should be thought of angio-Behçet syndrome. Choosing correct surgical treatment according to patient's condition and timing of pathological changes are the keys of gaining satisfactory results.