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Human arteries show structural and functional peculiarities according to the nutrient and oxygen needs of a specific vascular district. This architectural heterogeneity is reflected in the pathological setting of cardiovascular diseases (CVDs). Indeed, the responsiveness to cardiovascular risk factors, and the morphological and molecular patterns are discriminating factors among CVDs affecting different vascular beds. MicroRNAs (miRNAs) are endogenous regulators of gene expression and fine-tuners of vascular cell differentiation; thus, these non-coding RNAs can modulate arterial heterogeneity. The identification of an artery-specific miRNA signature would be promising in the therapy of CVDs, especially in patients who are frail and elderly. In the present review, we will provide a concise description of the arterial tree heterogeneity on a structural and cellular basis, mainly in the pathological context. Secondly, we will address the miRNA potential as crucial mediators of arterial heterogeneity, focusing on the abdominal aorta and femoral artery, with the final goal of strengthening the search for more targeted therapies in CVDs and stratification approaches in patients who are frail and elderly.

Intimal hyperplasia (IH) compromises the patency of arteriovenous fistula (AVF) vascular access in patients with end-stage kidney disease. Uncontrolled cell proliferation and migration, driven by inflammation, shear stress and surgery, are well-known triggers in IH. Recently, microRNAs (miRNAs) have emerged as regulators of core mechanisms in cardiovascular diseases and as potential markers of IH. This study was aimed at identifying a specific miRNA panel in failed AVFs and clarifying the miRNA involvement in IH. miRNA profiling performed in tissues from patients with IH (AVFs) and normal veins (NVs) highlighted a subset of four miRNAs significantly deregulated (hsa-miR-155-5p, hsa-miR-449a-5p, hsa-miR-29c-3p, hsa-miR-194-5p) between the two groups. These miRNAs were analyzed in tissue-derived cells (NVCs and AVFCs), human aortic smooth muscle cells (HAOSMCs) and human umbilical vein endothelial cells (HUVECs). The panel of hsa-miR-449a-5p, hsa-miR-155-5p, hsa-miR-29c-3p and hsa-miR-194-5p was up-regulated in AVFCs, HAOSMCs and HUVEC under inflammatory stimuli. Notably, overexpression of hsa-miR-449a-5p exacerbated the proliferative, migratory and inflammatory features of AVFCs. In vitro pharmacological modulation of these miRNAs with pioglitazone, particularly the down-regulation of hsa-miR-155-5p and hsa-miR-29c-3p, suggested their involvement in IH pathogenesis and a potential translational application. Overall, these findings provide new insights into the pathogenesis of AVF failure, reinforcing the miRNA contribution to IH detection and prevention.

IntroductionIntimal sarcomas are aggressive mesenchymal tumors arising from the tunica intima of large vessels, mainly the pulmonary artery. They are usually associated with MDM2 amplification. Due to their rarity and scarce sensitivity to chemotherapy, they are characterized by late diagnosis and high mortality. Thus, there is an urgent need to unravel novel therapeutic biomarkers. This study explored the role of the immune infiltrate and molecular profile in an intimal sarcoma cohort to evaluate their amenability to immunotherapy and detect potential targets, apart from MDM2.MethodsWhole transcriptome and whole exome sequencing were performed on 5 intimal sarcoma cases (FFPE) followed by computational analyses, including immune cell profiling, differential gene expression, variant calling and copy number alteration detection. ResultsAll samples presented the amplification of MDM2, confirming their diagnosis, and the co-amplification of CPM and SLC35E3. Interestingly, they also showed PD-L1 expression along with a prevalence of CD4+ memory resting T-cells, M2 macrophages and different concentrations of naïve B-cells, CD8+ T-cells and monocytes. The upregulation of immunoglobulins and pathways involved in the immune response (e.g. IL6/JAK/STAT3 and TNF-α via NF-kB signaling, interferon gamma response) further suggested a potential sensitivity to immunotherapy.DiscussionOur findings provided basic evidence for immunotherapy efficacy in intimal sarcomas and identified potential molecular targets. Further studies involving larger case series are required to validate these results.

Leiomyosarcoma of the inferior vena cava (IVC) is a rare and aggressive malignancy, with poor prognosis and no universally accepted treatment protocol. We present the case of a 69-year-old male with an IVC leiomyosarcoma, which extended from the common iliac veins to the right renal vein. Initial imaging showed a retroperitoneal mass with suspected IVC involvement. Histopathological examination confirmed leiomyosarcoma, and the patient underwent four chemotherapy cycles with doxorubicin, followed by surgical resection. A multidisciplinary approach, including general, vascular, and urologic surgeons, was employed. The tumor was excised en bloc with the IVC and right kidney. No prosthetic IVC reconstruction was necessary due to the lack of hemodynamic changes after clamping. Postoperative recovery was uneventful except for mild renal impairment. Molecular profiling of the tumor using next-generation sequencing (NGS) identified mutations in TP53, RB1, KMT2C, TSC2, and other genes associated with chromatin stability and tumor suppression. The patient experienced a local recurrence at four months and was treated with chemotherapy. This case underscores the importance of personalized treatment strategies, including surgical decision-making, chemotherapy, and molecular characterization, in managing rare tumors like IVC leiomyosarcoma. Further research is needed to explore potential oncogenic targets and improve prognosis.

The endothelial to mesenchymal transition (End–MT) can be associated with vascular calcification, by providing mesengenic progenitors. In this study, we investigated a link between End–MT and the osteogenic process and explored the involvement of miR-30a-5p and miR-30d as potential regulators of these processes. End–MT was induced in Human Umbilical Vein Endothelial Cells (HUVEC) through transforming growth factor-β1 (TGF-β1), TGFβ-3 and tumor necrosis factor-α (TNF-α), for 24 h and 6 days. End–MT mediators, mesenchymal and osteo/chondrogenic markers were analyzed through Real-Time PCR, immunofluorescence, flow cytometry and Western Blot. miR-30a-5p and miR-30d over-expression was carried out in HUVEC to explore their effects on End–MT and osteogenic differentiation. HUVEC at 24 h and 6 days gained mesenchymal morphology markers, including matrix metalloproteinase 9 (MMP-9), SLUG, VIMENTIN and α-smooth muscle actin (α-SMA), and a significant migratory potential, notably with TNF-α. After 6 days, the osteo/chondrogenic markers runt-related transcription factor 2 (RUNX-2) and SRY box transcription factor 9 (SOX-9) were upregulated. At this time point, miR-30a-5p and miR-30d decreased. Over-expression of miR-30a-5p and miR-30d affected End–MT mediators and the osteogenic potency in HUVEC, by reducing SLUG, VIMENTIN and RUNX-2. Our data suggest that End–MT represents a key link between inflammation and vascular calcification. Further, miR-30a-5p and miR-30d can regulate both the End–MT and the osteogenic processes, prompting future studies for exploring their potential use as therapeutic targets or biomarkers in vascular diseases.

Renal failure is a worldwide disease with a continuously increasing prevalence and involving a rising need for long-term treatment, mainly by haemodialysis. Arteriovenous fistula (AVF) is the favourite type of vascular access for haemodialysis; however, the lasting success of this therapy depends on its maturation, which is directly influenced by many concomitant processes such as vein wall thickening or inflammation. Understanding the molecular mechanisms that drive AVF maturation and failure can highlight new or combinatorial drugs for more personalized therapy. In this review we analysed the relevance of critical enzymes such as PI3K, AKT and mTOR in processes such as wall thickening remodelling, immune system activation and inflammation reduction. We focused on these enzymes due to their involvement in the modulation of numerous cellular activities such as proliferation, differentiation and motility, and their impairment is related to many diseases such as cancer, metabolic syndrome and neurodegenerative disorders. In addition, these enzymes are highly druggable targets, with several inhibitors already being used in patient treatment for cancer and with encouraging results for AVF. Finally, we delineate how these enzymes may be targeted to control specific aspects of AVF in an effort to propose a more specialized therapy with fewer side effects.

We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who developed an occlusive arterial disease of the lower limb requiring a left leg amputation. We studied the mechanisms of vascular damage by SARS-CoV-2 by means of a comprehensive multi-technique in situ analysis on the diseased popliteal arterial district, including immunohistochemistry (IHC), transmission electron microscopy (TEM) and miRNA analysis. At histological analyses, we observed a lymphocytic inflammatory infiltrate, oedema and endothelialitis of adventitial vasa vasorum while the media was normal and the intima had only minor changes. The vasa vasorum expressed the ACE2 receptor and factor VIII; compared with the controls, VEGFR2 staining was reduced. TEM analyses showed endothelial injury and numerous Weibel–Palade bodies in the cytoplasm. No coronavirus particle was seen. IL-6 protein and mRNA, together with miR-155-5p and miRs-27a-5p, which can target IL-6, were significantly increased compared with that in the controls. Our case report suggests an involvement of adventitial artery microcirculation by inflammation in the course of COVID-19. Without evident signs of current infection by SARS-CoV-2, endothelial cells show a spectrum of structural and functional alterations that can fuel the cardiovascular complications observed in people infected with SARS-CoV-2.

Background Popliteal artery aneurysms (PAAs) need urgent treatment in case of acute thrombosis, distal embolization, or rupture. Few data are available in the literature about the treatment results in these scenarios. The aim of the present study was to evaluate an 11-year multicenter experience in the urgent treatment of PAAs. Methods All symptomatic PAAs surgically treated in two vascular centers between 2010 and 2021 were retrospectively analyzed. In the postoperative period periodical clinical and Duplex-Ultrasound evaluation were performed. The evaluated endpoint was the outcome of urgent PAAs treatment according to their clinical presentation. Statistical analysis was performed by Kaplan-Meier log-rank evaluation and multivariable Cox regression tests. Results Sixty-six PAAs needed an urgent repair. Twelve (18%) patients had a PAA rupture and 54 (82%) had an acute limb ischemia (ALI) due to either distal embolization or acute thrombosis. Patients with ALI underwent bypass surgery in 51 (95%) cases, which was associated with preoperative thrombolysis in 18 (31%) cases. A primary major amputation was performed in 3 (5%) cases. The mean follow-up was 52 ± 21 months with an overall 5-year limb salvage of 83 ± 6%. Limb salvage was influenced only by the number of patent tibial arteries (pTA) [5-years limb salvage 0%, 86 ± 10%, 92 ± 8% and 100% in case of 0, 1, 2 or 3 pTA, respectively ( P  = .001)]. An independent association of number of pTA and limb loss was found [hazard ratio (HR): 0.14 (95% confidence interval (CI) 0.03–0.6), P  = .001]. Overall 5-year survival was 71 ± 7%. Ruptured PAAs were associated with lower 5-year survival compared with the ALI group (48 ± 2% vs. 79 ± 7%, P  = .001). The number of pTA (33 ± 20%, 65 ± 10%, 84 ± 10% and 80 ± 10% for 0, 1, 2 and 3 pTA, respectively, P  = .001) and the thrombolysis (94 ± 6% vs. 62 ± 10%, P  = .03) were associated with higher survival in patients with ALI. There was an independent association of number of pTA and long-term survival [HR 0.15 (95% CI 0.03–0.8), P  = .03]. Conclusions PAA rupture is the cause of urgent PAA treatment in almost one fifth of cases, and it is associated with lower long-term survival. ALI can benefit from thrombolysis, and long-term limb salvage and survival are associated with the number of pTA.

This narrative review aims to summarise the classification of vascular anomalies, their clinical presentation, and their radiological features to propose a diagnostic algorithm to approach patients with suspected soft tissue vascular anomalies of the extremities. The management of vascular anomalies necessitates a multidisciplinary approach. Clinical presentation and physical examination are sufficient in most cases to achieve a correct diagnosis. This is especially true for small congenital lesions of the skin and subcutaneous tissue. Imaging is used for accurate characterization of these lesions, especially in cases of atypical or vague clinical presentation, and to assess extension in cases of lesions that are larger and localized in deeper tissues.

Background: Endovascular aneurysm repair (EVAR) has become the primary choice of treatment for abdominal aortic aneurysm (AAA) and preventive intraoperative AAA sac embolization (SE) is an effective way to reduce endoleaks after EVAR. Preoperative planning of AAA SE has not been standardized yet, and typically requires a quite long and operator-dependent procedure using standard EVAR planning software. Methods: We introduce ‘EVAR-eaSE’, a software tool that we have developed to help vascular surgeons to plan the optimal SE procedure during EVAR, providing semi-automatic AAA segmentation and 3D modeling starting from patient scans, and then computing the aneurysm volumes. A preliminary accuracy evaluation on radiological phantoms, and a comparison with the commercial 3Mensio software for EVAR planning are carried out. Results: EVAR-eaSE software showed a good level of accuracy in aneurysm volume reconstruction and calculation (mean difference of 2.5% between real and segmented phantom volumes). A strong positive correlation (r = 0.940, r = 0.954, p < 0.001) was found between EVAR-eaSE computation of AAA Lumen and AAA Total volumes and the same measurements obtained with 3Mensio, for a database of 26 AAA cases. Conclusions: EVAR-eaSE demonstrated to be an easy-to-use, objective and accurate tool to assist the vascular surgeons in preoperative planning of SE during EVAR.