Empty vein ablation (EVA) technique: an in-vivo animal model to assess the effects of sclerosing agent concentration and wall contact time on intima and media tunicae structure.

BACKGROUND: Sclerotherapy is a cornerstone of the treatment of chronic venous disease, despite some technical aspects (e.g., sclerosant liquid agent concentration [SLAC] and contact time between sclerosant agent and vein wall [ctSA/VW]) to maximize outcomes remain an unsolved problem and a source of debate. An innovative three-balloon catheter has been developed to allow sclerotherapy in empty vein conditions (Empty Vein Ablation technique, EVA), revolutionizing the definition of SLAC and ctSA/VW. Aim of this experimental study is to analyze EVA effects on intima and media vessel tunicae using different SLAC and ctSA/VW in an in-vivo animal model. METHODS: Two adult sheep were treated by EVA using jugular and common iliac vein axes (eight vein segments). Different SLAC (polidocanol 0.5% or 1%) and different ctSA/VW (3 or 5 minutes) were combined for testing residual circumferential intima percentage and media thickness after EVA. RESULTS: Intact circumferential residual intima after the treatment was 21.3±4.9%, 18.2±7.4%, 15.7±2.4% and 8.9±2.0% using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.945; control sample: 97.6%). Media thickness after the treatment was 121.6±35.3 µm, 110.9±7.8 µm, 96.1±30.4 µm and 79.1±34.1 µm using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.990; control sample 125.7 µm). No significant modifications were detected analyzing the adventitia in all samples. CONCLUSIONS: EVA proved to be effective in venous wall destruction even with a very low SLAC and ctSA/VW (0.5% in 3 minutes), in quite large caliber veins. Direct comparisons with foam/liquid sclerotherapy should be done to confirm therapeutic effectiveness of these results, despite EVA has provided a maximized and controlled SA/VW contact time and ratio.

Acute shear stress and vein graft disease.

The long saphenous vein is commonly used in cardiac surgery to bypass occluded coronary arteries. Its use is complicated by late stenosis and occlusion due to the development of intimal hyperplasia. It is accepted that intimal hyperplasia is a multifactorial inflammatory process that starts immediately after surgery. The role of acute changes in haemodynamic conditions when the vein is implanted into arterial circulation, especially shear stress, is not fully appreciated. This review provides an overview of intimal hyperplasia and the effect of acute shear stress changes on the activation of pro-inflammatory mediators.

Intimal aortic atherosclerosis in cardiac surgery: surgical strategies to prevent embolic stroke.

OBJECTIVES: Although the incidence of perioperative stroke after cardiac surgery gradually decreased over the last decades, there is much variation between centres. This review aimed to create a concise overview of the evidence on possible surgical strategies to prevent embolic stroke in patients with intimal aortic atherosclerosis. METHODS: The PubMed and EMBASE databases were searched for studies on surgical management of aortic atherosclerosis and the association with perioperative stroke in cardiac surgery, including specific searches on the most common types of surgery. Articles were screened with emphasis on studies comparing multiple strategies and studies reporting on the patients' severity of aortic atherosclerosis. The main findings were summarized in a figure, with a grade of the corresponding level of evidence. RESULTS: Regarding embolic stroke risk, aortic atherosclerosis of the tunica intima is most relevant. Although several strategies in general cardiac surgery seem to be beneficial in severe disease, none have conclusively been proven most effective. Off-pump surgery in coronary artery bypass grafting should be preferred with severe atherosclerosis, if the required expertise is present. Although transcatheter aortic valve replacement is used as an alternative to surgery in patients with a porcelain aorta, the risk profile concerning intimal atherosclerosis remains poorly defined. CONCLUSIONS: A tailored approach that uses the discussed alternative strategies in carefully selected patients is best suited to reduce the risk of perioperative stroke without compromising other outcomes. More research is needed, especially on the perioperative stroke risk in patients with moderate aortic atherosclerosis.

[Surgical treatment of acute aortic syndrome: an update]. / Trattamento chirurgico della patologia aortica acuta: un update.

The term "acute aortic syndrome" describes a variety of acute and emerging aortic pathologies that include intramural hematoma, penetrating aortic ulcer and acute aortic dissection. However, the acute pathology of the thoracic aorta also includes the contained ruptures of aortic aneurysms, traumatic aortic ruptures and iatrogenic aortic dissections. In all these acute situations, in which emerging surgical treatment is often required, decision-making represents a crucial and extremely important phase, which often affects the patient's prognosis, in the short and long term. This review aims to present an update of the surgical treatment of acute aortic syndrome focusing mainly on the correct decision-making, the factors that influence it and the latest novel surgical techniques and strategies.

Intimal sarcoma of the pulmonary artery without 18F-fluorodeoxyglucose uptake.

Primary pulmonary intimal sarcoma is rare. Differentiating it from pulmonary thromboembolism is difficult because of similarities in clinical symptoms and imaging findings. Positron-emission tomography-computed tomography has been useful for diagnosing primary pulmonary intimal sarcoma. We describe a rare case of primary pulmonary intimal sarcoma that showed no abnormal 18F-fluorodeoxyglucose uptake on positron-emission tomography. We resected the mass and performed right ventricular outflow tract reconstruction. Proper diagnosis is necessary to determine appropriate therapy, Clinicians must consider the possibility of primary pulmonary intimal sarcoma even if imaging findings are inconsistent with the disease.

External Stents for Vein Grafts in Coronary Artery Bypass Grafting: Targeting Intimal Hyperplasia.

INTRODUCTION: Progressive saphenous vein graft (SVG) failure remains a key limitation to the long-term success of coronary artery bypass grafting (CABG). SVG disease after the first year is dominated by intimal hyperplasia, which predisposes the SVG to thrombosis and accelerated atherosclerosis. The objective of this study was to review and summarize the latest experimental and clinical data on the use of mechanical external stents for vein grafts. METHODS: In January 2020, the PubMed database was searched using the terms "external stent", "CABG", "saphenous vein graft" and "intimal hyperplasia". The results were reviewed and only randomized experimental and clinical studies that analyzed the effect of external stenting on venous intimal hyperplasia were included in the analysis, together with studies that investigated the clinical benefit of external stenting. RESULTS: Eight experimental and four clinical trials met the search criteria. Controlled trials in different large animal models concluded that external stenting significantly reduced intimal hyperplasia 3-6 months post implantation, and reduced both thrombosis rates and the development of lumen irregularities. Data from randomized controlled trials with a follow-up period of 1-4.5 years supported the pre-clinical findings and demonstrated that external stents significantly reduced vein graft disease. CONCLUSION: Strong evidence indicates that supporting the vein with external stents is safe and leads to clear advantages at both the anatomical and cellular levels. With the further accumulation of consistent positive results, external stenting of SVG may become the standard of care in future CABG.

Aortic angioscopy assisted thoracic endovascular repair for chronic type B aortic dissection.

BACKGROUND: Non-obstructive general angioscopy is a powerful modality for detecting areas in the aorta with vulnerable plaque, which are difficult to visualize using conventional diagnostic tools such as computed tomography (CT). The aim of the present study was to clarify the efficacy and usefulness of aortic angioscopy in patients with chronic type B aortic dissection scheduled for thoracic endovascular repair (TEVAR). METHODS: Ten patients with chronic type B aortic dissection who underwent elective TEVAR were enrolled. Before starting the stent graft procedure, the aortic intima was observed by use of non-obstructive general angioscopy. Based on those findings, the range of the stent graft position was confirmed. RESULTS: In all patients, observations of the aortic intima with non-obstructive general angioscopy from a point just proximal of the descending aorta to the iliac artery were successful. At the proximal site, an entry site or ulcer-like projection was detected in all patients, while a small intimal tear or entry, or an irregular intima surface with a salmon-pink color were seen in some cases. In contrast, preoperative CT did not detect any such findings in the same locations. After confirming the position of the abnormal intima, we determined the position of the distal end of the stent graft. No complications considered to be related to aortic angioscopy were noted. CONCLUSIONS: Non-obstructive general angioscopy is useful for observing the condition of the aortic intima, revealing abnormal conditions, and confirming a normal aortic intima in patients with chronic type B aortic dissection. This modality may play an important role in determining the precise position of a stent graft for a TEVAR procedure.

The Layer Where the Coronary Arterial "Endarterectomy" Specimen Separates from the Underlying Artery.

Described herein is a patient who had a coronary endarterectomy at the time of coronary artery bypass grafting. Histologic study of cross-sections of the endarterectomy specimen disclosed that the layer of separation of the endarterectomy specimen from the underlying native artery was in the media. This layer or plane of excision is virtually always the media irrespective of the artery having the endarterectomy. The procedure might better be called "endomediaectomy?"

Alterations in Surgically Created Intimal Lesions: An Observation Study in the Aortic Rat Model.

BACKGROUND: Intimal injury in microvessels due to common risk factors such as atherosclerosis or inadequate manipulation are known to have a major impact on developing thrombosis and eventually vascular obstruction. Understanding of these injuries is therefore of great significance to prevent far-reaching consequences such as flap loss in free tissue transfer. It was the aim of this study to evaluate artificially induced intimal lesions with focus on alteration in size and configuration. METHODS: Intimal defects were created surgically in the abdominal aorta of 30 male Wistar rats. After planimetric measurement of the defect sizes, configuration of defects were classified as round, horizontal, or vertical. Seven days postoperatively, the rats underwent a second-look surgery. Finally, the abdominal aorta was harvested, and the endothelial defects were reevaluated concerning size and configuration using a defined pattern. RESULTS: The mean defect size created intraoperatively was 1.68 ± 0.6 mm2. The classification of the defects configurations resulted in 43.3% round, 20% horizontal, and 36.7% vertical defects. Reevaluation at 7 days after surgery showed defect shrinkage in 96.7% in total and 42.8% averaging due to reendothelialization. A shift in defect configuration was detected in 56.7%, the strongest being in vertical defect configurations (100%). Vascular occlusion did not occur in any of the specimen. CONCLUSION: Intimal injuries undergo a fast repair process in terms of size reduction and configuration modification due to reendothelialization. Especially vertical defects, representing a great risk for thrombus formation, convert into lower risk horizontal defect configurations. In high-flow vessels such as the rat aortas, small endothelial damage seems to have no significant impact to produce complete vascular occlusion. Still, all efforts should be made to avoid any kind of intimal injury.

Oral Resolvin D1 attenuates early inflammation but not intimal hyperplasia in a rat carotid angioplasty model.

Inflammation ensuing from vascular injury promotes intimal hyperplasia (IH) and restenosis. Resolvin D1 (RvD1) is a lipid mediator that attenuates IH in vivo when delivered locally to the vessel wall in animal models. We tested the hypothesis that peri-procedural oral administration of RvD1 could blunt the local inflammatory response to angioplasty, and attenuate downstream IH. Carotid angioplasty was performed on rats fed with either RvD1 or vehicle through oral gavage, starting one day prior to injury until post-operative day (POD) 3 or 14 when arteries were harvested. To study pharmacokinetics and bioactivity of oral RvD1, we measured plasma RvD1 by ELISA, whole blood phagocytosis activity using flow cytometry, and cAMP levels in the thoracic aorta by ELISA. Carotid arteries were harvested on POD3 for staining (anti-CD45, anti-Myeloperoxidase (MPO), anti-Ki67 or dihydroethidium (DHE) for reactive oxygen species), mRNA expression of target genes (quantitative RT-PCR), or on POD14 for morphometry (elastin stain). RvD1 plasma concentration peaked 3 h after gavage in rats, at which point we concurrently observed an increase in circulating monocyte phagocytosis activity and aortic cAMP levels in RvD1-treated rats vs. vehicle. Oral RvD1 attenuated local arterial inflammation after angioplasty by reducing CD45+, MPO+, Ki67+ cells, and DHE staining intensity. Oral RvD1 also reduced the expression of several pro-inflammatory genes within the injured vessels. However, oral RvD1 did not significantly reduce IH. Oral RvD1 attenuated acute inflammation within the arterial wall after angioplasty in rats, but did not significantly affect IH.

Remodeling of a Cell-Free Vascular Graft with Nanolamellar Intima into a Neovessel.

Advances in cardiovascular materials have brought us improved artificial vessels with larger diameters for reducing adverse responses that drive acute thrombosis and the associated complications. Nonetheless, the challenge is still considerable when applying these materials in small-diameter blood vessels. Here we report the biomimetic design of an acellular small-diameter vascular graft with specifically lamellar nanotopography on the luminal surface via a modified freeze-cast technique. The experimental findings verify that the well-designed nanolamellar structure is able to inhibit the adherence and activation of platelets, induce oriented growth of endothelial cells, and eventually remodel a neovessel to maintain long-term patency in vivo. Furthermore, the results of numerical simulations in physically mimetic conditions reveal that the regularly lamellar nanopattern can manipulate blood flow to reduce the flow disturbance compared with random topography. Our current work not only creates a freeze-cast small-diameter vascular graft that employs topographic architecture to direct the vascular cell fates for revasculature but also rekindles confidence in biophysical cues for modulating in situ tissue regeneration.

Descending aortic replacement for intimal angiosarcoma.

Aortic angiosarcoma is an exceedingly rare clinical entity. A significant delay in diagnosis can occur due to its rareness and lack of specific clinical manifestation. A 71-year-old woman was admitted to the emergency department owing to an acute episode of abdominal pain. A computed tomography (CT) scan showed thoraco-abdominal aortic occlusion and splenic infarction. The patient was initially treated with descending aortic replacement for degenerative atherothrombotic aneurysm. An FDG-positron emission tomography-CT scan and biopsy ultimately confirmed the diagnosis of aortic angiosarcoma. This case highlights the difficulties of making an early diagnosis of aortic angiosarcoma.

Idiopathic myointimal hyperplasia is a distinct cause of chronic colon ischaemia.

AIM: Colon ischaemia (CI) is most commonly an acute and reversible manifestation of a transient, non-occlusive decrease of blood flow in the colonic microvasculature. Irreversible complications are uncommon and the progression to chronic CI remains controversial. Our objective was to identify cases of chronic CI and assess for distinct clinicopathological features. METHOD: A retrospective review was performed of CI patients having symptom chronicity of ≥ 1 month and ischaemic histology at our institution from 1994 to 2015. Demographic, clinical, endoscopic, radiological, pathological and outcome variables were abstracted. Histological evaluation was performed by two gastrointestinal pathologists. RESULTS: Fifteen patients (n = 9; 67% men) with a median age of 65 years (range 22-88) were identified. The most common presenting symptoms were diarrhoea and abdominal pain (n = 6, 86%; n = 5, 71%, respectively). The typical endoscopic appearance was segmental ulceration of the sigmoid colon (n = 6, 75%). Vascular imaging showed patent mesenteric vessels in all patients. Histopathological evaluation revealed venous intimal hyperplasia consistent with idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) in eight patients; the remainder showed non-specific ulceration and fibrosis. Surgical resection was performed in seven IMHMV patients, resulting in symptom resolution. On re-review of pre-resection biopsies, all IMHMV patients had characteristic changes of hyperplastic, thick-walled, hyalinized vessels in the lamina propria. CONCLUSIONS: IMHMV is a unique histopathological entity causing chronic CI. The small vessel histological changes in IMHMV are distinctive in colonic resections and undetectable by routine vascular imaging. Preoperative diagnosis of IMHMV is possible with endoscopic biopsy and segmental colon resection is curative.

Differential impact of intimal tear location on aortic dilation and reintervention in acute type I aortic dissection after total arch replacement.

OBJECTIVE: The study objective was to evaluate the differential impact of intimal tear location on aortic dilation and reintervention after total arch replacement for acute type I aortic dissection. METHODS: From 2009 to 2016, 85 patients underwent total arch replacement for acute type I aortic dissection with residual dissected thoracoabdominal aorta. Forty patients (47%) underwent serial computed tomography scans that were sufficient for analysis. Among these, 14 (35%) underwent total arch replacement via the frozen elephant trunk procedure. Intimal tears were analyzed (size and number) at 3 different levels (level 1, proximal descending thoracic aorta; level 2, distal descending thoracic aorta; level 3, abdominal aorta). Aortic diameter was measured at 4 levels (pulmonary artery bifurcation, celiac axis, maximal abdominal aorta, and maximal thoracoabdominal aorta) using serial follow-up computed tomography scans. The linear mixed model for a repeated-measures random intercept and slope model was used. The rate of freedom from reintervention was analyzed. RESULTS: In the unadjusted analysis, initial diameter of pulmonary artery bifurcation level, number of intimal tears, presence of 3- or 5-mm intimal tears, and frozen elephant trunk were not significant factors for aortic dilation or shrinking. The significant factors for aortic dilation were intimal tear location and number of visceral branches from the false lumen. The 3-year freedom from reintervention rate was significantly higher in patients with intimal tears 3 mm or greater at level 3 than in those with tears at level 1 (94.1% vs 37.5%, log-rank, P < .001). CONCLUSIONS: Intimal tear in the proximal descending thoracic aorta is the most important factor for aortic dilation and reintervention in acute type I aortic dissection after total arch replacement.

Enterocolic lymphocytic phlebitis with marked myointimal hyperplasia and perivenous concentric fibrosis.

Enterocolic lymphocytic phlebitis (ELP) is a rare enteropathy characterized by lymphocytic phlebitis of the mesenteric veins without arteritis. Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare disease similar to ELP, characterized by myointimal hyperplasia that constricts the lumen of veins, causing mucosal injury. A 62-year-old man with chief complaint of abdominal pain was treated by partial resection of the ileum after 3 months of conservative therapy. The pathologic diagnosis was ELP with prominent myointimal hyperplasia. Histologically, the lesion consisted of lymphocytic infiltration into the vein accompanied by prominent myointimal hyperplasia and perivenous concentric fibrosis, which are characteristics shared by ELP and IMHMV. The observations in this case suggest that some of ELP and IMHMV may belong to the same disease spectrum. Furthermore, perivascular concentric fibrosis was a remarkable observation that may contribute to differential diagnosis between ELP and "true" IMHMV.

Untreated distal intimal tears may be associated with paraplegia after total arch replacement and frozen elephant trunk treatment of acute Stanford type A aortic dissection.

OBJECTIVE: To investigate the possible overlooked causes of early postoperative paraplegia, a severe complication of acute Stanford type A aortic dissection (ATAAD) after total arch replacement and frozen elephant trunk (FET). METHODS: We reviewed the clinical data and perioperative aortic computed tomography angiography records of 110 consecutive patients with ATAAD who underwent total arch replacement and FET (12 cm) between December 2014 and September 2017 and investigated the possible risk factors related to early postoperative paraplegia. RESULTS: Paraplegia occurred in 5 (4.5%) patients. No significant differences were found between patients with and without paraplegia in terms of sex, age, medical history, cardiopulmonary bypass time, antegrade cerebral perfusion time, rectal temperature during antegrade cerebral perfusion, postoperative hypotension, maximum first 24-hour vasoactive-inotropic score, upper-lower pressure gradient, or false lumen thrombosis. Postoperative aortic computed tomography angiography showed a "cutoff" phenomenon in the lower descending aorta in 4 of the 5 patients. Univariate logistical analysis showed that paraplegia was associated with the "cutoff" phenomenon (P < .05). The patients with a distance ≥30 mm from the distal end of the stent to the first untreated intimal tear had significantly greater rates of the "cutoff" phenomenon and paraplegia than those with the distance <30 mm (P < .05). CONCLUSIONS: Total arch replacement and FET is safe and feasible for ATAAD involving the descending aorta. Early postoperative paraplegia is associated with the "cutoff" phenomenon in the lower descending aorta. The position of the first untreated intimal tear may be related with the occurrence of the "cutoff" phenomenon and paraplegia.

Catheter-Directed Fenestration for Branch Vessel Reconnection in Aortic Dissection Using a Novel Diamond-Tipped Chronic Total Occlusion Drilling Device: A Technical Report.

PURPOSE: Aortic dissection is a complex condition with high morbidity and mortality. Endovascular treatments including percutaneous fenestration can be used to manage branch vessel ischaemia or risk of aortic rupture. A variety of techniques for aortic fenestration have been described. We describe the novel use of the TruePath Chronic Total Occlusion (CTO) device for aortic intimal fenestration to achieve side branch reconnection. MATERIALS AND METHODS: We present three cases of aortic dissection presenting with symptoms of aortic side branch occlusion and end organ malperfusion, treated with aortic fenestration using the TruePath CTO device via trans-brachial and trans-femoral approaches. RESULTS: Technical success was achieved in all three cases. No complications were encountered. Flow was restored in compromised visceral branches. Branches remained patent on follow-up CT angiography over a minimum 2.5-year follow-up period. CONCLUSION: Percutaneous aortic fenestration techniques enable a minimally invasive approach to treat visceral branch malperfusion associated with aortic dissection. The TruePath CTO device improves the control of the fenestration procedure with the potential to improve efficacy and safety.

Surgical outcomes of acute type A aortic dissection in dialysis patients.

BACKGROUND: Acute type A aortic dissection (ATAAD) is relatively uncommon in dialysis patients, and characteristics and repair outcomes are not fully understood. PATIENTS AND METHODS: Patients with ATAAD (n = 960) were divided into a dialysis group (n = 19) and non-dialysis group (n = 941), depending on whether they required dialysis for preoperative end-stage renal disease (ESRD). Hospital charts and imaging data were reviewed, and characteristics and outcomes were compared between the groups. Segmental aortic wall or intima/media flap calcification in the thoracic and abdominal aorta was assessed in the dialysis patients. RESULTS: The leading primary causes of ESRD were polycystic kidney disease (n = 5) and chronic glomerulonephritis (n = 5). There were no significant differences (dialysis group vs. non-dialysis group) in age (60.5 vs. 64.5 years), preoperative hemodynamics, or organ ischemia. Dialysis patients were more likely to have an entry tear in the aortic arch (42% vs. 15%, p = 0.003). These patients showed moderate-to-severe calcification (multiple focal or single focal calcification > 10 mm) in the ascending aorta (17%), aortic arch (61%), descending aorta (67%), and abdominal aorta (83%). Arch replacement was common in this group (37% vs. 18%, p = 0.030). Although in-hospital mortality was increased in this group (21% vs. 7%, p = 0.059), morbidities did not differ significantly. Six-year survival was 60.3 ± 13.4% and 78.8 ± 1.6%, respectively (p = 0.01). CONCLUSIONS: Dialysis patients tend to have aortic calcification and a primary tear in the aortic arch. Outcomes are acceptable.

A New Technique to Induce Experimental Myointimal Hyperplasia.

BACKGROUND: Arterial myointimal hyperplasia (MIH) has a significant impact on the long-term outcomes of vascular procedures such as bypass surgery and angioplasty. In this study, we describe a new and innovative technique to induce MIH using a dental flossing cachet in Wistar rats. METHODS: The intimal damage in the common carotid artery was induced by inserting the tip of the dental flossing cachet through the external carotid artery into the common carotid artery and turning it on for 3 rounds of 20 s each (n = 10). After 2 weeks, the rats were anesthetized and the common carotid arteries of the experimental side and the contralateral side (control) were harvested and preserved for histopathological studies. RESULTS: The experimental carotid arteries showed significant intimal proliferation and thickening compared to the controls. The intima/media ratio of the experimental and normal (control) common carotid arteries were 1.274 ± 0.162 and 0.089 ± 0.023 (mean ± SEM), respectively (p < 0.001). CONCLUSION: This technique is simple, inexpensive, and highly reproducible and it induces sufficient MIH to study this phenomenon in animal models.

Down-regulation of vascular GLP-1 receptor expression in human subjects with obesity.

It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expression in human arteries in immunostaining. Next, we separated the artery into the intima and media, and evaluated gene expression levels of various factors. We divided the subjects into obesity and non-obesity group and compared their expression levels between them. Finally, we evaluated which factors determine vascular GLP-1 receptor expression. GLP-1 receptor expression in intima and media was lower in obesity group compared to non-obesity group which was correlated with the alteration of TCF7L2 expression. Multiple regression analyses showed that BMI was an independent determining factor for GLP-1 receptor expression in the intima and media. Furthermore, using small interfering RNA method and TCF7L2-EGFP adenovirus, we showed that TCF7L2 was involved in GLP-1 receptor expression in human vascular cells. Taken together, vascular GLP-1 receptor and TCF7L2 expression was significantly down-regulated in human subjects with obesity. In addition, it is likely that TCF7L2 functions as a modulator of vascular GLP-1 receptor expression.