Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs.

One of the early symptoms of chronic venous disease (CVD) is varicose veins (VV) of the lower limbs. There are many etiological environmental factors influencing the development of chronic venous insufficiency (CVI), although genetic factors and family history of the disease play a key role. All these factors induce changes in the hemodynamic in the venous system of the lower limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity of matrix metalloproteinases (MMPs), changes in microcirculation and, consequently, the remodeling of the venous wall. The aim of this review is to present current knowledge on CVD, including the pathophysiology and mechanisms related to vein wall remodeling. Particular emphasis has been placed on describing the role of inflammation and oxidative stress and the involvement of extracellular hemoglobin as pathogenetic factors of VV. Additionally, active substances used in the treatment of VV were discussed.

Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis.

Importance: Multiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice. Objective: To quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI). Design, Setting, and Participants: This was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants' diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2). Exposures: MS/CIS vs non-MS conditions. Main Outcomes and Measures: Area under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model. Results: The presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P < .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis. Conclusions and Relevance: The findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

Paramagnetic rim lesions and the central vein sign: Characterizing multiple sclerosis imaging markers.

BACKGROUND AND PURPOSE: Paramagnetic rims and the central vein sign (CVS) are proposed imaging markers of multiple sclerosis (MS) lesions. Using 7 tesla magnetic resonance imaging, we aimed to: (1) characterize the appearance of paramagnetic rim lesions (PRLs); (2) assess whether PRLs and the CVS are associated with higher levels of MS pathology; and (3) compare the characteristics between subjects with and without PRLs in early MS. METHODS: Prospective study of 32 treatment-naïve subjects around the time of diagnosis who were assessed for the presence of PRLs and the CVS. Comparisons of lesion volume and macromolecular pool size ratio (PSR) index, a proxy of myelin integrity, between PRLs and non-PRLs, and CVS-positive and CVS-negative lesions were carried out. Differences in clinical/demographic characteristics between patients with PRLs and those without were tested. RESULTS: Fifteen subjects had ≥1 PRL for a total of 36 PRLs, of which two-thirds had a full rim. PRLs predicted a larger lesion size and decreased PSR signal. Lesion volume and presence of cervical spine lesions were significantly different between subjects with PRLs and those without, although neither remained significant after adjusting for multiple comparisons. One hundred and eighty-one lesions with CVS were identified with no differences between CVS-positive and CVS-negative lesions in volume (p = .27) and PSR values (p = .62). CONCLUSIONS: PRLs, but not CVS-positive lesions, are larger and have lower myelin integrity. Our findings indicate that PRLs are associated with higher levels of lesion-specific pathology prior to the start of disease-modifying therapy.

Cavernous venous malformations in and around the central nervous system. Part 1: Dural and extradural.

Cavernous-type malformations are venous lesions that occur in multiple locations throughout the body, and when present in the CNS, they have canonically been referred to as cavernomas, cavernous angiomas, and cerebral cavernous malformations. Herein all these lesions are referred to as "cavernous venous malformations" (CavVMs), which is congruent with the current International Society for the Study of Vascular Anomalies classification system. Even though histologically similar, depending on their location relative to the dura mater, these malformations can have different features. In Part 1 of this review, the authors discuss and review pertinent clinical knowledge with regard to CavVMs as influenced by anatomical location, starting with the dural and extradural malformations. They particularly emphasize dural CavVMs (including those in the cavernous sinus), orbital CavVMs, and spinal CavVMs. The genetic and histopathological features of CavVMs in these locations are reviewed, and commonalities in their presumed mechanisms of pathogenesis support the authors' conceptualization of a spectrum of a single disease entity. Illustrative cases for each subtype are presented, and the pathophysiological and genetic features linking dural and extradural to intradural CavVMs are examined. A new classification is proposed to segregate CavVMs based on the location from which they arise, which guides their natural history and treatment.

Establishment and study of a rat internal haemorrhoid model.

To establish a relatively stable internal haemorrhoid model in rats. A total of 48 SPF SD rats were selected and randomly divided into a blank group of 16 and a model group of 32. The model was created by croton oil-mixed liquid stimulation combined with standing and swimming experiments, and the modelling times were 1 week and 2 weeks, respectively. By observing the symptoms and signs of rats, pathological morphology and immunohistochemical staining of anorectal tissue, anorectal laser speckle blood-flow imaging and defecation contrast, etc., the effect of different modelling times was evaluated. The stability of the model was evaluated after feeding for 2 weeks. Both model-formation times caused rats to produce local symptoms of tissue bulging in the haemorrhoid area. Microscopy showed that the rectal submucosal interstitial blood vessels were dilated, and inflammatory cell infiltration and other manifestations were observed. Laser speckle blood-flow imaging revealed increased anorectal blood perfusion and capillary dilatation, and defecography showed a longitudinal and continuous rectal mucosa. After 2 weeks of normal feeding, lifting of the haemorrhoidal tissue was still present. The effect of modelling for 1 week was most in line with the clinical manifestations of internal haemorrhoids. The 1-week modelling scheme in this study can effectively establish a rat internal haemorrhoid model that closely approximates clinical internal haemorrhoid symptoms and pathological manifestations. The operation is simple, the success rate is high, and the model has certain stability. This model can be used as an important basis for studying various treatment methods for internal haemorrhoids.

Rare Oral Hemangioma in Pregnancy: A Case Series Providing Clinical Insight into Patient Care.

BACKGROUND Hemangiomas are defined as benign soft tissue vascular tumors that are histologically classified as capillary, cavernous, or mixed types. Hemangiomas can also be described based on clinical appearance as superficial, mixed, or deep lesions. Following a thorough search, only 3 case reports of superficial protruding lip mass were found in the literature. Other cases of tongue hemangioma have been reported in infants or young toddlers, and only rarely in adults. CASE REPORT The first case was a 43-year-old pregnant woman, with an unremarkable medical and surgical history, in the second trimester who presented to the Otolaryngology Clinic with a chief concern of a progressively growing lesion, measuring 0.7×0.5 cm, over the lateral right side of the tongue for the last 2 weeks after accidentally biting her tongue during dinner. The second case was a 26-year-old woman with unremarkable medical and surgical history who presented to our Otolaryngology Clinic with a chief concern of a non-painful soft fungating pink-red lip lesion 1.5×1 cm across the right lower lip growing for the last 4 months. This lesion appeared during the third trimester of pregnancy following a lip injury that was described as minor trauma. CONCLUSIONS Although hemangiomas can occur anywhere on the body, they are most commonly found in the head and neck. These lesions are usually recognized quickly by patients and treating physicians and are thus clinically diagnosed. Most vascular benign lesions regress on their own, but if detected early, they are surgically excised for cosmetic and functional reasons.

Supracerebellar Infratentorial Approach, Indications, and Technical Pitfalls.

Posterior tentorial incisura not infrequently requires to be exposed for tumors of pineal gland, pulvinar, midbrain and cerebellum, aneurysms, arteriovenous malformations. Residing almost at the center of the brain, this area is almost equal distance to any point on the calvarium behind coronal sutures enabling alternative routes to encounter. Compared to supratentorial routes either subtemporal or suboccipital approach, infratentorial supracerebellar route has several advantages as providing shortest, most direct approach to the lesions of this area without encountering any important arteries and veins. Since its initial description at the early twentieth century, a wide range of complications arising from cerebellar infarction, air embolism, and neural tissue damage have been encountered. Working in a deep, narrow corridor without enough illumination and visibility under very limited anesthesiology support hindered popularization of this approach. In the contemporary era of neurosurgery, advanced diagnostic tools and surgical microscopes with state-of-the-art microsurgery techniques coupled with modern anesthesiology have eliminated almost all drawbacks of infratentorial supracerebellar approach.

Venous malformations of the lower limb with severe localized intravascular coagulopathy treated with radiofrequency ablation and resection.

Diffuse venous malformations (VMs) are relatively rare, especially the lesions locting special anatomical sites, and they are prone to casuse localized intravascular coagulopathy (LIC). Diffuse VMs can also cause bleeding and life-threatening disseminated intravascular coagulopathy (DIC) from trauma, surgery, and improper treatments. Thus, the treatment of diffuse VMs with LIC is quite tough. We report of a diffuse VMs with severe LIC that was treated with the combined use of minimally invasive treatment and open surgery.

Photochemically Aided Arteriovenous Fistula Creation to Accelerate Fistula Maturation.

Rates of arteriovenous fistula maturation failure are still high, especially when suboptimal size veins are used. During successful maturation, the vein undergoes lumen dilatation and medial thickening, adapting to the increased hemodynamic forces. The vascular extracellular matrix plays an important role in regulating these adaptive changes and may be a target for promoting fistula maturation. In this study, we tested whether a device-enabled photochemical treatment of the vein prior to fistula creation facilitates maturation. Sheep cephalic veins were treated using a balloon catheter coated by a photoactivatable molecule (10-8-10 Dimer) and carrying an internal light fiber. As a result of the photochemical reaction, new covalent bonds were created during light activation among oxidizable amino acids of the vein wall matrix proteins. The treated vein lumen diameter and media area became significantly larger than the contralateral control fistula vein at 1 week (p = 0.035 and p = 0.034, respectively). There was also a higher percentage of proliferating smooth muscle cells in the treated veins than in the control veins (p = 0.029), without noticeable intimal hyperplasia. To prepare for the clinical testing of this treatment, we performed balloon over-dilatation of isolated human veins and found that veins can tolerate up to 66% overstretch without notable histological damage.

Molecular Determinants of Chronic Venous Disease: A Comprehensive Review.

Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins of lower limbs causing a wide range of symptoms and signs with a high prevalence in the general population and with disabling consequences in the most severe forms. The etiology and pathophysiology of CVD is complex and multifactorial, involving genetic, proteomic, and cellular mechanisms that result in changes to the venous structure and functions. Expressions of several genes associated with angiogenesis, vascular development, and the regulation of veins are responsible for the susceptibility to CVD. Current evidence shows that several extracellular matrix alterations (ECM) could be identified and in some cases pharmacologically targeted. This review shows the most up to date information on molecular determinants of CVD in order to provide a complete overview of the current knowledge on this topic. In particular, the article explores the genetic influence, the hormonal influence, ECM imbalance, and histopathology of CVD and the role of endothelial dysfunction in CVD.

Intravenous Lobular Capillary Hemangioma of the Neck: A Report of 2 Cases.

Background: Intravenous lobular capillary hemangioma (IVLCH) of the neck is a kind of rare benign tumor of vein. Purpose: In this paper, we report two female patients who were hospitalized because of neck masses. Results: The tumors in the neck veins of our patients were white oval masses with pedicle, clearly defined and of different sizes. Their immunohistochemical staining results showed CD31 (+), CD34 (+), SMA (+), ERG (+). The pathological diagnosis was intravenous lobular capillary hemangioma. Conclusions: Due to the location, morphology and immunohistochemistry, This lesion needs to be distinguished from other intravascular lesions such as thrombus, hemangiosarcoma and papillary endothelial hyperplasia.

The role of alpha-1-antitrypsin in the etiopathogenesis of chronic venous disease: A prospective clinical trial.

OBJECTIVE: The study aimed to examine whether alpha-1-antitrypsin (AAT), an inhibitor of leukocyte esterase(LE), which damages the venous vessel wall, has a protective effect against chronic venous disease(CVD), and to examine the relationship between AAT levels and disease severity. METHODS: Patients admitted with varicose vein disease and having reflux flow lasting longer than 0.5 s as determined by Doppler ultrasound were included. The informed consents were taken, and blood samples were obtained for complete blood count, C-reactive protein (CRP) level, and AAT level following anamnesis and physical examination. Clinical Etiologic Anatomic Pathologic (CEAP) classification was used to assess disease severity, and patients were divided into CEAP 1-5 groups accordingly. RESULTS: A total of 87 patients were included in the study. There was no statistically significant difference between the groups in body weight, red blood cell counts, platelet counts, or neutrophil counts (p = 0.117, p = 0.932, p = 0.177, and p = 0.177, respectively).CRP and AAT levels were higher in patients with a CEAP clinical score of 5 compared to the other groups (p = 0.018, and p = 0.020, respectively). AAT levels were similar in the CEAP 1-3 group and decreased in the CEAP-4 group but increased again in the CEAP-5 group. The AAT level was 1.62 ± 0.3 g/L in the CEAP-1 group, 1.61 ± 0.21 g/L in the CEAP-2 group, 1.61 ± 0.27 g/L in the CEAP-3 group, 1.48 ± 0.28 g/L in the CEAP-4 group, and 1.94 ± 0.39 g/L in the CEAP-5 group. CRP levels and platelet counts were observed to affect AAT levels (p = 0.10, p = 0.017, respectively). CONCLUSION: We believe that our hypothesis that low AAT levels play a role in the etiopathogenesis of CVD has been partially validated, at least in the CEAP-4 group. However, we believe that increased AAT levels in the CEAP-5 group may be a reactive increase in increased LE levels due to higher CRP levels of this group.

A snapshot of early venous remodeling in a 7-day-old arteriovenous fistula.

Early remodeling of the arteriovenous fistula (AVF) determines maturation outcomes. However, the cellular response of the venous wall early after AVF creation remains largely enigmatic because of the lack of venous biopsies obtained shortly after anastomosis. This report presents a detailed immunohistochemistry analysis of a pre-access cephalic vein and the resulting seven-day-old AVF that required ligation due to steal syndrome. We test for markers of mature and progenitor endothelial cells (CD31, CD34, VWF), contractile smooth muscle cells and myofibroblasts (MYH11, SMA), and immune cell populations (CEACAM8, CD3, CD20, CD11b, CD45, CD68, CD163, tryptase). We demonstrated near complete endothelial coverage of the fistula at 7 days, a high degree of wall neovascularization, pronounced loss of myofibroblasts and smooth muscle cells, and significant infiltration of mast cells, neutrophils, monocytes, and macrophages. Of interest, the presence of CD163+ macrophages in the AVF suggests a reactive response to increased intramural oxygenation. In conclusion, these images provide for the first time a glimpse of early remodeling in a human AVF by immunohistochemistry. This case demonstrates the possibility to obtain additional precious samples of this early stage through future multicenter collaborative efforts.

Tissue Ki67 proliferative index expression and pathological changes in hemodialysis arteriovenous fistulae: Preliminary single-center results.

BACKGROUND: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes. MATERIALS AND METHODS: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots. RESULTS: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0-65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 (p = 0.001) and with NA (p = 0.001). CONCLUSIONS: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.

Central Vein Sign in Multiple Sclerosis: A Comparison Study of the Diagnostic Performance of 3T versus 7T MRI.

BACKGROUND AND PURPOSE: An early and accurate diagnosis of multiple sclerosis remains challenging in clinical neurology. Established diagnostic methods have less than desirable sensitivity and specificity. An accurate, noninvasive diagnostic test for MS could have a major impact on diagnostic criteria. We compared the frequency of detection of the central vein sign (CVS) in white matter lesions of MS and controls on 7T T2*-weighted and SWI to 3T SWI. Additionally, we assessed the diagnostic performance of 7T T2*, 7T SWI, and 3T SWI for MS. MATERIALS AND METHODS: A retrospective case-control study was performed of patients with MS having both 7T MRI and 3T MRI. A control group of patients without MS was selected. Diagnosis of MS was established by board-certified neurologists with fellowship training in autoimmune neurology in line with the 2017 McDonald criteria. Percentage of lesions with a CVS was blindly measured for each technique. Diagnostic performance was computed by sensitivity, specificity, and positive and negative likelihood ratios (LRs). RESULTS: Sixty-one patients with MS (903 lesions) and 39 controls (1088 lesions) were included. 7T T2* showed significantly more CVS (87%) than both 7T SWI (73%) and 3T SWI (31%) (all P < .001). CVS was identified in the control group in ≤6% of lesions on all sequences. Using a threshold of >40% of lesions with CVS on 7T T2* and >15% on 7T SWI, both sequences had an accuracy = 100%, sensitivity = 100%, specificity = 100%, infinite positive LR, and zero negative LR. Using an optimal threshold of >12%, 3T SWI had an accuracy = 96.0%, sensitivity = 93.4%, specificity = 100%, infinite positive LR, and negative LR = 0.066. CONCLUSIONS: 7T MRI had 100% sensitivity and specificity for the diagnosis of MS and is superior to 3T. Future revisions to MS diagnostic criteria may consider recommendations for 7T MRI and inclusion of CVS as a biomarker.

Silhouette Lymphangioma: An Unknown Macular Form of Cutaneous Lymphangioma.

Unusual angiomatous or lymphangiomatous vascular malformations are rarely seen. One of them is lymphangioma (LA), which is a rare benign lymphovascular abnormality. LA is usually seen in the types of circumscriptum (or capillary), cavernous and cystic. Here, we report a unique case of LA with a patchy appearance. The patient presented due to unusual symptoms and eccentric clinical manifestation of the lesion. Here, we present a new lymphatic entity which was diagnosed as LA with its clinical, radiological and pathological findings. Written informed consent of the patient was obtained for this report. To the best of our knowledge this macular form of cutaneous LA has not been previously reported in literature. Macular LA should be kept in mind when faced with a colored long-term macular lesion on the skin.

A clinicopathological reappraisal of orbital vascular malformations and distinctive GJA4 mutation in cavernous venous malformations.

Vascular anomalies are common orbital lesions, while variations in previous nomenclature might hamper robust characterization of their clinicopathological and genetic features. We reviewed and reclassified 92 orbital vascular lesions by the modified International Society for the Study of Vascular Anomalies (ISSVA) classification with reappraising clinicopathological parameters of 4 main types of vascular malformations, including orbital venous malformation 1 (OVM1, cavernous venous malformation), OVM2 (varix), OVM3 (infiltrating venous malformation), and arteriovenous malformation (AVM). GJA4, BRAF, and KRAS mutations were assessed by Sanger sequencing. There were 90 cases of vascular malformations, consisting of 60 OVM1 (67%), 13 AVM (14%), 8 OVM2 (9%), 8 OVM3 (9%), and 1 lymphatic-venous malformation (1%). The prevailing OVM1, histologically characterized by well-delineated borders and a uniform cavernous growth pattern, predominantly occurred in intraconal space (57%, P = .019) with an older median age (49 years) and female predilection (73%). OVM2, OVM3, and AVM exhibited differences in the distributions of patients' ages and lesion locations. Sizes of lesions were significantly correlated with periorbital and intraconal/extraconal locations (P < .001). OVM1 had the lowest rate of residual and recurrent diseases (3%). GJA4 mutations were identified in 75% (44/59) of OVM1 but not in OVM2/3 and AVM. No BRAF or KRAS mutations were detected. In conclusion, the modified ISSVA scheme enables meaningful classification of orbital vascular malformations by highlighting the molecular correlation between the distinct clinicopathological features and specific GJA4 mutation in OVM1, which implies OVM1 as a unique variant of venous malformation genetically akin to cutaneous and hepatic counterparts.

Biodegradable external wrapping promotes favorable adaptation in an ovine vein graft model.

Vein grafts, the most commonly used conduits in multi-vessel coronary artery bypass grafting surgery, have high intermediate- and long-term failure rates. The abrupt and marked increase in hemodynamic loads on the vein graft is a known contributor to failure. Recent computational modeling suggests that veins can more successfully adapt to an increase in mechanical load if the rate of loading is gradual. Applying an external wrap or support at the time of surgery is one way to reduce the transmural load, and this approach has improved performance relative to an unsupported vein graft in several animal studies. Yet, a clinical trial in humans has shown benefits and drawbacks, and mechanisms by which an external wrap affects vein graft adaptation remain unknown. This study aims to elucidate such mechanisms using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, hemodynamics using computational fluid dynamics, structure using histology, and transcriptional changes using bulk RNA-sequencing in an ovine carotid-jugular interposition vein graft model, without and with an external biodegradable wrap that allows loads to increase gradually. We show that a biodegradable external wrap promotes luminal uniformity, physiological wall shear stress, and a consistent vein graft phenotype, namely, it prevents over-distension, over-thickening, intimal hyperplasia, and inflammation, and it preserves mechanotransduction. These mechanobiological insights into vein graft adaptation in the presence of an external support can inform computational growth and remodeling models of external support and facilitate design and manufacturing of next-generation external wrapping devices. STATEMENT OF SIGNIFICANCE: External mechanical support is emerging as a promising technology to prevent vein graft failure following coronary bypass graft surgery. While variants of this technology are currently under investigation in clinical trials, the fundamental mechanisms of adaptation remain poorly understood. We employ an ovine carotid-jugular interposition vein graft model, with and without an external biodegradable wrap to provide mechanical support, and probe vein graft adaptation using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, fluid flow using computational fluid dynamics, vascular composition and structure using histology, and transcriptional changes using bulk RNA sequencing. We show that the wrap mitigates vein graft failure by promoting multiple adaptive mechanisms (across biological scales).