Late Treatment Failure after Stenting and Percutaneous Aspiration for Adventitial Cystic Disease in the Popliteal Artery: A Follow-up Case Report.

Adventitial cystic disease (ACD), a rare vascular disease characterized by mucus accumulation in the adventitia of blood vessels, typically affects the popliteal artery. We present the case of a 61-year-old female diagnosed with ACD in 2018 who was initially treated with endovascular stenting and percutaneous aspiration of the cyst. The patient, who had been asymptomatic for 5 years, developed a stent fracture and pseudoaneurysm requiring surgical intervention. Despite initial successful treatment, complications such as stent fracture and recurrence can occur; therefore, surgical treatment is recommended to optimize outcomes in patients with ACD. Endovascular treatment and cyst aspiration should only be considered in cases with high surgical risk. After treatment, long-term follow-up and individualized management strategies are important to monitor ACD recurrence.

Relationship Between Early and Established Rheumatoid Arthritis Vascular Change of the Dorsalis Pedis Artery Observed with Ultrasound Imaging.

BACKGROUND: Despite early treatment of rheumatoid arthritis (RA) being well established to prevent erosive joint damage, studies report persistent moderate to high disease activity. Other pathologies, for example, rheumatoid vasculitis (RV) may contribute symptoms that may not be captured by existing clinical assessment. OBJECTIVES: To investigate ultrasound-observed changes in the proximal dorsalis pedis artery (DPA) between early (≤ 5 y) and established (>5 y) RA and the RA Disease Activity Index-5 (RADAI-5). METHODS: Participants with early (n = 20) and established RA (n = 20) were recruited. Five parameters of the DPA were examined with a previously established ultrasound method. Independent t-tests and Cohen d statistics assessed differences and effect size between ultrasound parameters and RADAI-5, and the two groups. Pearson correlation assessed associations between ultrasound parameters and RADAI-5. RESULTS: Majority of participants (98%) demonstrated arterial wall thickening regardless of disease duration. However, lumen diameter (Cohen's d = 0.972, p = 0.004) and artery diameter (Cohen's d = 0.694, p = 0.034) were decreased in established RA compared to early RA. No strong associations were found between RADAI-5 and ultrasound parameters, except for lumen diameter in early RA demonstrating a fair association to RADAI-5 (r = 0.445). The mean RADAI-5 score indicated moderate to high disease activity with no difference between early and established RA (p = 0.283). CONCLUSION: Arterial wall thickening of the DPA indicating the precursory changes of RV was observed in most RA participants, with reductions in artery and lumen diameter occurring in established disease. However, the long-standing instrument RADAI-5 may not reflect symptoms and clinical impacts related to vascular changes among people with RA.

Non-small cell lung cancer cells and concomitant cancer therapy induce a resistance-promoting phenotype of tumor-associated mesenchymal stem cells.

Introduction: The tumor microenvironment gained attraction over the last decades as stromal cells significantly impact on tumor development, progression and metastasis, and immune evasion as well as on cancer therapy resistance. We previously reported that lung-resident mesenchymal stem cells (MSCs) were mobilized and activated in non-small cell lung cancer (NSCLC) progression and could even mediate radiation resistance in co-cultured NSCLC cells. Methods: We investigated how MSCs were affected by NSCLC cells in combination with cancer (radiation) therapy in indirect co-cultures using tumor-conditioned medium and Transwells or direct three-dimensional NSCLC-MSC spheroid co-cultures in order to unravel the resistance-mediating action of tumor-associated MSCs. Results: Although no obvious phenotypic and functional alterations in MSCs following NSCLC co-culture could be observed, MSC senescence was induced following co-applied radiotherapy (RT). Global gene expression profiling, in combination with gene set enrichment analysis upon treatment, was used to confirm the senescent phenotype of irradiated MSC and to reveal relevant senescence-associated secretory phenotype (SASP) factors that could meditate NSCLC RT resistance. We identified senescent tumor-associated MSC-derived serine proteinase inhibitor (serpin) E1/PAI1 as potential SASP factor mediating NSCLC progression and RT resistance. Discussion: Specified intra-tumor-stroma interactions and cell type-specific pro-tumorigenic functions could not only improve lung cancer classification but could even be used for a more precise profiling of individual patients, finally paving an additional way for the discovery of potential drug targets for NSCLC patients.

Integrated transcriptomics of human blood vessels defines a spatially controlled niche for early mesenchymal progenitor cells.

Human blood vessel walls show concentric layers, with the outermost tunica adventitia harboring mesenchymal progenitor cells. These progenitor cells maintain vessel homeostasis and provide a robust cell source for cell-based therapies. However, human adventitial stem cell niche has not been studied in detail. Here, using spatial and single-cell transcriptomics, we characterized the phenotype, potential, and microanatomic distribution of human perivascular progenitors. Initially, spatial transcriptomics identified heterogeneity between perivascular layers of arteries and veins and delineated the tunica adventitia into inner and outer layers. From this spatial atlas, we inferred a hierarchy of mesenchymal progenitors dictated by a more primitive cell with a high surface expression of CD201 (PROCR). When isolated from humans and mice, CD201Low expression typified a mesodermal committed subset with higher osteogenesis and less proliferation than CD201High cells, with a downstream effect on canonical Wnt signaling through DACT2. CD201Low cells also displayed high translational potential for bone tissue generation.

The 3D organ-on-a-chip model unveils a dual role of GDF-15 in vascular growth.

Pathological conditions such as oxidative stress or inflammation may alter the homeostasis of adventitia triggering vascular wall remodeling and abnormal angiogenesis, what can lead to development of atherosclerosis. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and metabolic regulator, but its role in angiogenesis is not yet fully defined. Here we utilized an organ-on-a-chip technology to analyze endothelial sprouting in an adventitia-resembling microenvironment. We analyzed angiogenic responses to growth factor gradient across the extracellular matrix-resembling fibrin gel and in cell co-culture in response to GDF-15-treated adventitial fibroblasts. We observed that GDF-15 enhanced the pro-angiogenic effect of vascular endothelial growth factor. On the other hand, GDF-15-treated adventitial fibroblasts decreased endothelial sprouting. GDF-15 seems to indirectly affect endothelial cells and, depending on the microenvironment, its effect can be either pro- or anti-angiogenic.

Ultrasound imaging of the dorsalis pedis artery as an early indicator of the precursory changes for rheumatoid vasculitis: A case series.

Introduction: Clinical verification of rheumatoid vasculitis (RV) persists as a mid-to-late diagnosis with medical imaging or biopsy. Early and subclinical presentations of RV, in particular, can remain underdiagnosed in the absence of adequate diagnostic testing. In this study, the research demonstrated the precursory changes for RV in patients with rheumatoid arthritis (RA) using non-invasive ultrasound imaging of a peripheral vessel. Method: Six participants were recruited: three participants with (RA) and three age- and gender-matched healthy controls. All participants completed a Foot Health Survey Questionnaire (FHSQ), and participants with RA completed a Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5). Bilateral B-mode and Doppler ultrasound of the dorsalis pedis artery (DPA) was performed. The degree of inflammation, lumen and artery diameters, lumen diameter-to-artery diameter ratio and peak systolic velocity in the proximal DPA were compared between the two groups. Results: The mean RADAI-5 score (5.4 ± 0.8 out of 10) indicated moderate disease activity amongst participants with RA. Inflammation was observed in the DPA wall in all participants with RA, compared to no inflammation observed in the control group (Friedmans two-way analysis: χ2 = 15.733, P = 0.003). Differences between groups for inflammation, lumen diameter and lumen diameter-to-artery diameter ratio were found (P < 0.034), without differences for artery diameter and peak systolic velocity (P > 0.605). DPA wall inflammation did not correlate with FHSQ scores (r = -0.770, P = 0.073). Conclusion: Despite moderate RA disease activity, this is the first study to demonstrate the use of ultrasound to observe inflammation in small vessel disease. Our findings suggest ultrasound imaging may be a viable screening tool to demonstrate arterial wall inflammation, indicating the precursory changes of RV.

Cystic adventitial disease of the popliteal artery: A case report with review of literature.

INTRODUCTION AND IMPORTANCE: Cystic adventitial disease (CAD) is a rare vascular disorder marked by occlusion stemming from the development of a cystic mass within the outer (subadventitial) layer, with a predominant impact on the popliteal artery. The significance of the case presented herein lies in shedding light on a distinct clinical manifestation involving a 40-year-old man who exhibited sporadic calf claudication during ambulation. This instance contributes to the broader understanding of CAD and its diverse clinical presentations, emphasizing the need for further exploration and awareness within the medical community. CASE PRESENTATION: A 40-year-old man, with no significant past medical history, was referred to the cardiovascular department for the evaluation of a new onset of left calf pain persisting over the past three months. An arterial lower limb Doppler ultrasound was performed, revealing a focal hypoechoic image around the popliteal artery with a regular arterial wall, indicative of extrinsic compression. This resulted in significant stenosis of the popliteal artery during plantar flexion of the foot. The diagnosis of CAD of the left popliteal artery was established after limb computed tomography angiography, and a complete resection of the cyst was scheduled. The postoperative course was uneventful, with the patient experiencing relief from left calf claudication. CLINICAL DISCUSSION: CAD is an uncommon vascular anomaly, representing merely 0.1 % of all vascular conditions. This condition predominantly afflicts men aged between 40 and 50 years old. The etiology of CAD remains a subject of debate, with pathological findings typically involving intramural cysts containing gelatinous material between the media and the adventitia. Surgical intervention becomes necessary when symptoms arise. CONCLUSION: CAD of the popliteal artery, though rare, is a significant contributor to peripheral vascular insufficiency in young patients without typical atherosclerotic risk factors.

Effect of Ultraviolet Radiation on the Enzymolytic and Biomechanical Profiles of Abdominal Aortic Adventitia Tissue.

BACKGROUND: The abdominal aortic aneurysm (AAA) is defined as an increase in aortic diameter by more than 50% and is associated with a high risk of rupture and mortality without treatment. The aim of this study is to analyze the role of aortic adventitial collagen photocrosslinking by UV-A irradiation on the biomechanical profile of the aortic wall. METHODS: This experimental study is structured in two parts: the first part includes in vitro uniaxial biomechanical evaluation of porcine adventitial tissue subjected to either short-term elastolysis or long-term collagenolysis in an attempt to duplicate two extreme situations as putative stages of aneurysmal degeneration. In the second part, we included biaxial biomechanical evaluation of in vitro human abdominal aortic adventitia and human AAA adventitia specimens. Biomechanical profiles were examined for porcine and human aortic tissue before and after irradiation with UV-A light (365 nm wavelength). RESULTS: On the porcine aortic sample, the enhancing effect of irradiation was evident both on the tissue subjected to elastolysis, which had a high collagen-to-elastin ratio, and on the tissue subjected to prolonged collagenolysis despite being considerably depleted in collagen. Further, the effect of irradiation was conclusively demonstrated in the human adventitia samples, where significant post-irradiation increases in Cauchy stress (longitudinal axis: p = 0.001, circumferential axis: p = 0.004) and Young's modulus (longitudinal axis: p = 0.03, circumferential axis: p = 0.004) were recorded. Moreover, we have a stronger increase in the strengthening of the AAA adventitia samples following the exposure to UV-A irradiation (p = 0.007) and a statistically significant but not very important increase (p = 0.021) regarding the stiffness in the circumferential axis. CONCLUSIONS: The favorable effect of UV irradiation on the strength and stiffness of degraded aortic adventitia in experimental situations mimicking early and later stages of aneurysmal degeneration is essential for the development and potential success of procedures to prevent aneurysmal ruptures. The experiments on human normal and aneurysmal adventitial tissue confirmed the validity and potential success of a procedure based on exposure to UV-A radiation.

Perivascular Adipose Tissue Remodels Only after Elevation of Blood Pressure in the Dahl SS Rat Fed a High-Fat Diet.

INTRODUCTION: Tunica media extracellular matrix (ECM) remodeling is well understood to occur in response to elevated blood pressure, unlike the remodeling of other tunicas. We hypothesize that perivascular adipose tissue (PVAT) is responsive to hypertension and remodels as a protective measure. METHODS: The adventitia and PVAT of the thoracic aorta were used in measuring ECM genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% Kcal fat) or high-fat (HF; 60%) diet. A PCR array of ECM genes was performed with cDNA from adventitia and PVAT after 8 and 24 weeks. A gene regulatory network of the differentially expressed genes (DEGs) (HF 2-fold > con) was created using Cytoscape. RESULTS: After 8 weeks, 29 adventitia but 0 PVAT DEGs were found. By contrast, at 24 weeks, PVAT possessed 47 DEGs while adventitia had 3. Top DEGs at 8 weeks in adventitia were thrombospondin 1 and collagen 8a1. At 24 weeks, thrombospondin 1 was also a top DEG in PVAT. The transcription factor Adarb1 was identified as a regulator of DEGs in 8-week adventitia and 24-week PVAT. CONCLUSION: These data support that PVAT responds biologically once blood pressure is elevated.

Venous adventitial cystic disease is a very rare disease that can cause deep vein thrombosis: A case report.

BACKGROUND: Venous adventitial cystic disease (VACD) is a rare disease characterized by cysts, filled with a gelatinous mucous substance similar to joint fluid, in the adventitia of blood vessels adjacent to the joints. It is often misdiagnosed as deep vein thrombosis (DVT), femoral varices, venous tumors, or lymphadenopathy. CASE SUMMARY: A 69-year-old woman visited our hospital with a complaint of swelling in the right lower extremity. The patient was diagnosed with DVT and prescribed apixaban at an outpatient clinic. After 3 wk, the patient was hospitalized again because of sudden swelling in the right lower extremity. We diagnosed VACD and performed surgery for cyst removal as well as patch angioplasty and thrombectomy of the right common femoral vein. The patient received anticoagulants for 6 mo and has been doing well without recurrence for 1 year postoperatively. CONCLUSION: Recurrent VACD requires complete removal of the connections to the joint cavity to prevent recurrence.

Determinants of vascular structure and function in at-risk children born to mothers managed for pre-eclampsia (FINNCARE study).

Background and aim: Pre-eclampsia (PE) is related to elevated blood pressure (BP) in children. The study aims to investigate if elevated BP is reflected in child arterial health and how anthropometrics, body composition, and gestational and perinatal factors influenced this. Methods: In this prospective cohort study, we assessed the arteries of 182 children exposed (46 had an early onset, with a diagnosis before 34 gestational weeks, and 136 had a late onset) and 85 children unexposed (non-PE) to PE at 8-12 years from delivery using ultra-high-frequency ultrasound in addition to ambulatory and central BPs, body composition and anthropometrics, and tonometry-derived pulse wave velocity (PWV). Results: No differences were found in intima-media thickness (IMT), adventitia thickness (AT), lumen diameter (LD), local carotid artery stiffness, distensibility, or wall stress between PE-exposed and non-PE-exposed children. All children's brachial, radial, and femoral artery IMTs were associated with 24-h systolic BP (SBP) and pulse pressure, carotid-femoral PWV, and anthropometric measures. The 24-h SBP and anthropometrics, notably lean body mass, were independent predictors of peripheral artery IMTs (brachial R2 = 0.217, radial R2 = 0.208, femoral R2 = 0.214; p < 0.001). Head circumference predicted carotid artery IMT and LD (ß = 0.163, p = 0.009; ß = 0.417, p < 0.001, respectively), but carotid artery IMT was not associated with BP. No independent associations were found for peripheral artery ATs. Local carotid artery stiffness, distensibility, and wall stress were independently associated with adiposity. No significant associations were found between gestational or perinatal factors and child vascular health parameters. Conclusions: The peripheral artery IMT of PE-exposed children is identical to that of non-PE-exposed children, but associated with BP. Adiposity is related to local carotid artery stiffness. These adverse associations in arterial health may reflect the early progression of cardiovascular disease in PE-exposed children.

Efficacy of novel, three jaw adventitia holding microclamps compared to Acland microclamps in patients undergoing end-to-end microvascular anastomosis: A randomized control trial.

OBJECTIVE: To evaluate the efficacy of three jaw adventitia holding (TADH) microclamps in end-to-end microvascular anastomosis. BACKGROUND: Acland clamps, though highly efficacious, require a steep learning curve and are associated with complications such as back walling and incomplete bites. METHODS: A single center, parallel group, 30-patient randomized clinical trial was conducted with a 1:1 allocation ratio in Acland and TADH microclamp groups. Primary outcome was time taken for microvascular anastomosis in terms of arterial and venous clamping and suturing time. Secondary outcomes included ease of use, need for clamp flipping and adventitia trimming, and need for assistance and flap survival. RESULTS: TADH microclamps were found to be beneficial when compared to Acland microclamps in end-to-end microvascular anastomosis, in terms of artery clamp time (19.07 ± 3.751 min, 95% CI 10.058-17.942, p < 0.001), artery suture time (15.87 ± 3.357 min, 95% CI 10.660-17.206, p < 0.001), vein clamp time (21.50 ± 3.849 min, 95% CI 12.131-19.469, p < 0.001), and vein suture time (16.58 ± 3.147 min, 95% CI 13.232-20.368, p < 0.001). The TADH microclamps did not require flipping to enable suturing of the posterior walls of the vessel. Statistically significant difference was found in surgeon-reported ease of use with TADH microclamps (Chi-square value 9.867, p < 0.001). Statistically significant difference was found in relation to the need for assistance with TADH microclamps (Chi-square value 19.286, p < 0.001). CONCLUSION: This study found TADH microclamps to be faster, easier to use, and clinically efficacious in reducing the anastomosis time compared to those of the Acland clamps.

Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification.

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.

The microenvironment of the atheroma expresses phenotypes of plaque instability.

Data from histopathology studies of human atherosclerotic tissue specimens and from vascular imaging studies support the concept that the local arterial microenvironment of a stable atheroma promotes destabilizing conditions that result in the transition to an unstable atheroma. Destabilization is characterized by several different plaque phenotypes that cause major clinical events such as acute coronary syndrome and cerebrovascular strokes. There are several rupture-associated phenotypes causing thrombotic vascular occlusion including simple fibrous cap rupture of an atheroma, fibrous cap rupture at site of previous rupture-and-repair of an atheroma, and nodular calcification with rupture. Endothelial erosion without rupture has more recently been shown to be a common phenotype to promote thrombosis as well. Microenvironment features that are linked to these phenotypes of plaque instability are neovascularization arising from the vasa vasorum network leading to necrotic core expansion, intraplaque hemorrhage, and cap rupture; activation of adventitial and perivascular adipose tissue cells leading to secretion of cytokines, growth factors, adipokines in the outer artery wall that destabilize plaque structure; and vascular smooth muscle cell phenotypic switching through transdifferentiation and stem/progenitor cell activation resulting in the promotion of inflammation, calcification, and secretion of extracellular matrix, altering fibrous cap structure, and necrotic core growth. As the technology evolves, studies using noninvasive vascular imaging will be able to investigate the transition of stable to unstable atheromas in real time. A limitation in the field, however, is that reliable and predictable experimental models of spontaneous plaque rupture and/or erosion are not currently available to study the cell and molecular mechanisms that regulate the conversion of the stable atheroma to an unstable plaque.

Mechanisms of Coronary Artery Spasm.

Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal medical therapy. This has led to much more attention being paid to coronary vasomotion abnormalities regardless of obstructive or non-obstructive arterial segments. Coronary vasomotion is regulated by multiple mechanisms that include the endothelium, vascular smooth muscle cells (VSMCs), myocardial metabolic demand, autonomic nervous system and inflammation. Over the years, several animal models have been developed to explore the central mechanism of coronary artery spasm. This review summarises the landmark studies on the mechanisms of coronary vasospasm demonstrating the central role of Rho-kinase as a molecular switch of VSMC hypercontraction and the important role of coronary adventitial inflammation for Rho-kinase upregulation in VSMCs.

Neointima abating and endothelium preserving - An adventitia-localized nanoformulation to inhibit the epigenetic writer DOT1L.

Open vascular reconstructions such as bypass are common treatments for cardiovascular disease. Unfortunately, neointimal hyperplasia (IH) follows, leading to treatment failure for which there is no approved therapy. Here we combined the strengths of tailoring nanoplatforms for open vascular reconstructions and targeting new epigenetic mechanisms. We produced adhesive nanoparticles (ahNP) that could be pen-brushed and immobilized on the adventitia to sustainably release pinometostat, an inhibitor drug selective to the epigenetic writer DOT1L that catalyzes histone-3 lysine-79 dimethylation (H3K79me2). This treatment not only reduced IH by 76.8% in injured arteries mimicking open reconstructions in obese Zucker rats with human-like diseases but also avoided the shortcoming of endothelial impairment in IH management. In mechanistic studies, chromatin immunoprecipitation (ChIP) sequencing revealed co-enrichment of the histone mark H3K27ac(acetyl) and its reader BRD4 at the gene of aurora kinase B (AURKB), where H3K79me2 was also enriched as indicated by ChIP-qPCR. Accordingly, DOT1L co-immunoprecipitated with H3K27ac. Furthermore, the known IH driver BRD4 governed the expression of DOT1L which controlled AURKB's protein level, revealing a BRD4- > DOT1L- > AURKB axis. Consistently, AURKB-selective inhibition reduced IH. Thus, this study presents a prototype nanoformulation suited for open vascular reconstructions, and the new insights into chromatin modulators may aid future translational advances.

Proposal for T3 classification of esophagogastric junction carcinoma based on the interconnection of extramural anatomical structures.

Classification of extramural invasion of esophagogastric junction carcinoma (EGJC) is not yet established. The anatomy surrounding the EGJ alters between the mediastinum and the abdominal cavity. This review proposed a T3 classification of EGJC based on anatomical continuity. Analysis of endoscopic ultrasound images, review of intraoperative images, and detailed observation of surgical specimens were followed by a review of the literature. In the EGJ, the muscularis propria of the esophagus is enclosed in mediastinal adipose tissue called the adventitia, which is surrounded by the diaphragmatic crus and contains the paraesophageal lymph nodes (LNs). After passing through the esophageal hiatus along with the vagus nerves and blood vessels, the adventitia joins the adipose tissue containing the paracardial LNs, which is covered by the peritoneum, and then further divides into the lesser and greater omentum. The connective tissue outside the muscularis propria of the stomach, including the adipose tissue of the omentum, is called the subserosa. According to the TNM classification, T3 esophageal and gastric cancer is defined as invasion of the adventitia and subserosa, respectively. Given that the adventitia is anatomically continuous with the subserosa, T3 tumors of the EGJ can be described as those that extend through the muscularis propria but do not invade the peritoneum or diaphragmatic crus. We propose classifying T3 EGJC as "tumor extends through muscularis propria" rather than using the separate terms "adventitia" and "submucosa". T4 could be "tumor perforates serosa or invades adjacent structures", as per the current gastric cancer classification.

Evaluation of a multi-scale discrete fiber model for analyzing arterial failure.

So far, the prevalent rupture risk quantification of aortic aneurysms does not consider information of the underlying microscopic mechanisms. Uniaxial tension tests were performed on imaged aorta samples oriented in circumferential and longitudinal directions. To account for local heterogeneity in collagen fiber architecture, SHG imaging was performed on tissues at several locations prior to mechanical testing. This enabled the quantification of micro-scale information including organization of collagen fibers using relevant probability density functions. Two different modeling approaches are presented in this study for the sake of comparison. A multi-scale mechanical model was developed using this micro-structural information with collagen fibers as main components. accounting for non-affine fiber kinematics. Simultaneously, an embedded element model that accounts for affine fiber kinematics was developed in Abaqus using the same micro-structural information. Numerical simulations emulating uniaxial tension experiments were performed on the developed models. Global mechanical response of both models agreed well with the experimental data, although leading to mismatched material properties. The models present a rudimentary yet better than before representation of structure based description of aortic-tissue failure mechanics. reinforcing the importance of structural organization of micro-scale constituents and their kinematics in determining tissue failure.

Adventitial macrophage accumulation impairs perivascular nerve function in mesenteric arteries with inflammatory bowel disease.

Introduction: Inflammatory bowel disease involves aberrant immune responses and is associated with both cardiovascular disease risk and altered intestinal blood flow. However, little is known about how inflammatory bowel disease affects regulation of perivascular nerves that mediate blood flow. Previous work found perivascular nerve function is impaired in mesenteric arteries with Inflammatory bowel disease. The purpose of this study was to determine the mechanism of impaired perivascular nerve function. Methods: RNA sequencing was performed on mesenteric arteries from IL10-/- mice treated with H. hepaticus to induce disease (inflammatory bowel disease) or left non-gavaged (Control). For all other studies, Control and Inflammatory bowel disease mice received either saline or clodronate liposome injections to study the effect of macrophage depletion. Perivascular nerve function was assessed using pressure myography and electrical field stimulation. Leukocyte populations, and perivascular nerves, and adventitial neurotransmitter receptors were labeled using fluorescent immunolabeling. Results: Inflammatory bowel disease was associated with increases in macrophage-associated gene expression, and immunolabeling showed accumulation of adventitial macrophages. Clodronate liposome injection eliminated adventitial macrophages, which reversed significant attenuation of sensory vasodilation, sympathetic vasoconstriction and sensory inhibition of sympathetic constriction in inflammatory bowel disease. Acetylcholine-mediated dilation was impaired in inflammatory bowel disease and restored after macrophage depletion, but sensory dilation remained nitric oxide independent regardless of disease and/or macrophage presence. Conclusion: Altered neuro-immune signaling between macrophages and perivascular nerves in the arterial adventitia contributes to impaired vasodilation, particularly via dilatory sensory nerves. Targeting the adventitial macrophage population may help preserve intestinal blood flow in Inflammatory bowel disease patients.