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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Objective To explore a simple and feasible method for whole-mount immunofluorescence staining of lymphatic vessels in the ApoE-/- mouse model of atherosclerosis. Methods Aortic specimens were carefully excised from the ApoE-/- mouse model. Following immunostaining with specific antibodies against smooth muscle actin (SMA) and lymphatic vessel endothelial receptor 1 (LYVE1), the aortas, including the aortic root, were subjected to a 30-minute treatment with 5 g/L Sudan Black B solution. This step was instrumental in minimizing the autofluorescent background of the tissue. Thereafter, the aortas were processed through a clearing protocol and imaged within a purpose-built chamber under a fluorescence microscope. Results The pretreatment with 5 g/L Sudan Black B effectively suppressed the autofluorescent signals emanating from the vascular structures, thereby enhancing the contrast and clarity of the specific fluorescence signals associated with the lymphatic vessels. This enhancement in signal quality did not compromise the integrity or specificity of the immunofluorescent markers. Conclusion A facile, highly specific, and effective approach for the visualization of lymphatic vessels in whole-mount aortic preparations from ApoE-/- mice is established.

OBJECTIVE: It was previously believed that atherosclerotic (AS) plaque starts to develop from the intima and that intraplaque vasa vasorum (VV) hyperplasia promotes adventitial VV (AVV) hyperplasia. However, recent studies have shown that arterial AVV hyperplasia precedes early intimal thickening, suggesting its possible role as an initiating factor of AS. To provide further insight into this process, in this study, we examine the evolution of AAV and VV development in a preclinical model of early AS with longitudinal ultrasound imaging.
METHODS: Models of early AS were established. Duplex ultrasound scanning and contrast-enhanced ultrasound were performed for diagnosis. Pearson correlation tests were used to analyze the relationships between AVV hyperplasia and VV hyperplasia, or between AVV hyperplasia and intima-media thickness (IMT).
RESULTS: During 0-12 wk of high-fat feeding, AVV gradually increased and intima-media thickened gradually in the observation area; in the 2nd wk of high-fat feeding, the observation area showed obvious AVV proliferation; at the 4th wk, the intima-media membrane became thicker; at the 12th wk, early plaque formation and intraplaque VV proliferation were observed. There was a strong positive correlation between AVV proliferation and IMT thickening and a strong negative correlation between AVV proliferation and the change rate of vessel diameter.
CONCLUSIONS: This study demonstrated that AVV proliferation in the arteries occurred earlier than IMT thickening and was positively correlated with IMT. At present, the indicators of ultrasonic diagnosis of AS, such as IMT, Intraplaque VV, Echo property, all appear in the advanced stage of AS. The AVV may be an innovative diagnostic target for the early stage of AS plaque.

UNASSIGNED: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the world\'s population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis.
UNASSIGNED: This cross-sectional study aimed to explore the relationship between NAFLD severity, assessed via liver biopsy, and early atherosclerosis using adventitial vasa vasorum (VV) density. It included 44 patients with obesity (33 with steatosis, 11 with NASH) undergoing bariatric surgery.
UNASSIGNED: Results revealed no significant differences in adventitial VV density between steatosis and NASH groups, neither in the mean values [0.759 ± 0.104 vs. 0.780 ± 0.043, P=0.702] nor left-right sides. Similarly, carotid intima-media thickness (cIMT) did not vary between these groups. Additionally, no linear correlation existed between VV density and cIMT. Only gender showed an association with VV density.
UNASSIGNED: These findings suggest that NASH severity doesn\'t independently drive early atherosclerosis or affects cIMT. Gender might play a role in early atherosclerotic disease in NAFLD, impacting VV density and cIMT. This highlights the need to consider other risk factors when evaluating cardiovascular risk in NAFLD patients.

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UNASSIGNED: Cystic adventitial disease (CAD) is an uncommon condition that affects arteries and veins. It can cause a rare type of non-atherosclerotic peripheral vessel disease. The most common vessel affected is the popliteal artery. The number of case reports on CAD of the femoral artery is growing. We present a case of a 62-year-old female presented with claudication of the left leg diagnosed with CAD of the left common femoral artery. The patient was treated surgically with cyst excision and vessel reconstruction with saphenous vein autograft patch plasty. After 8-months the cyste relapsed and she had new claudication complains. We decided to perform new surgery. Surgical treatment consisted of cyst resection by excision of the femoral bifurcation and saphenous vein autograft interposition reconstruction of the bifurcation. We also provide an update on the latest literature of surgical treatment of CAD of the ilio-femoral artery region.
UNASSIGNED: Medline and EMBASE were used to collect articles on CAD of ilio-femoral artery. We included English written or translated case reports or series between 1987 and 2023.
UNASSIGNED: Twenty-nine patients out of 28 case reports were included. Most patients were male (59%). Claudication is the most common symptom (76%). Treatment consisted of cyst resection, cyst decompression, Endarterectomy, patch angioplasty and interposition graft using PTFE, Dacron, Great saphenous vein (GSV) or femoral vein autograft. Recurrence appeared in 4 cases (14%).
UNASSIGNED: In accordance to the literature and our experience we recommend complete vessel excision and saphenous vein (or PTFE) interposition bypass as treatment.

UNASSIGNED: 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.
METHODS: 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.
UNASSIGNED: 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.
CONCLUSIONS: CAD of the popliteal artery, though rare, is a significant contributor to peripheral vascular insufficiency in young patients without typical atherosclerotic risk factors.

Collagen fiber arrangement is decisive for constitutive description of anisotropic mechanical response of arterial wall. In this study, their orientation in human common carotid artery was investigated using polarized light microscopy and an automated algorithm giving more than 4·106 fiber angles per slice. In total 113 slices acquired from 18 arteries taken from 14 cadavers were used for fiber orientation in the circumferential-axial plane. All histograms were approximated with unimodal von Mises distribution to evaluate dominant direction of fibers and their concentration parameter. 10 specimens were analyzed also in circumferential-radial and axial-radial planes (2-4 slices per specimen in each plane); the portion of radially oriented fibers was found insignificant. In the circumferential-axial plane, most specimens showed a pronounced unimodal distribution with angle to circumferential direction μ = 0.7° ± 9.4° and concentration parameter b = 3.4 ± 1.9. Suitability of the unimodal fit was confirmed by high values of coefficient of determination (mean R2 = 0.97, median R2 = 0.99). Differences between media and adventitia layers were not found statistically significant. The results are directly applicable as structural parameters in the GOH constitutive model of arterial wall if the postulated two fiber families are unified into one with circumferential orientation.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.