Reversible Host-Guest Crosslinks in Supramolecular Hydrogels for On-Demand Mechanical Stimulation of Human Mesenchymal Stem Cells.

Stem cells are regulated not only by biochemical signals but also by biophysical properties of extracellular matrix (ECM). The ECM is constantly monitored and remodeled because the fate of stem cells can be misdirected when the mechanical interaction between cells and ECM is imbalanced. A well-defined ECM model for bone marrow-derived human mesenchymal stem cells (hMSCs) based on supramolecular hydrogels containing reversible host-guest crosslinks is fabricated. The stiffness (Young's modulus E) of the hydrogels can be switched reversibly by altering the concentration of non-cytotoxic, free guest molecules dissolved in the culture medium. Fine-adjustment of substrate stiffness enables the authors to determine the critical stiffness level E* at which hMSCs turn the mechano-sensory machinery on or off. Next, the substrate stiffness across E* is switched and the dynamic adaptation characteristics such as morphology, traction force, and YAP/TAZ signaling of hMSCs are monitored. These data demonstrate the instantaneous switching of traction force, which is followed by YAP/TAZ signaling and morphological adaptation. Periodical switching of the substrate stiffness across E* proves that frequent applications of mechanical stimuli drastically suppress hMSC proliferation. Mechanical stimulation across E* level using dynamic hydrogels is a promising strategy for the on-demand control of hMSC transcription and proliferation.

Risk and Prognosis of Upper Extremity Deep Vein Thrombosis.

Objectives: We aimed to investigate the clinical features of upper extremity deep vein thrombosis (UEDVT). Methods: We retrospectively reviewed the background, thrombus site, treatment, and outcome of 76 UEDVT patients. Results: Of the 76 UEDVT patients, 44 (57.9%) were men, and 51 (67.1%) were complicated by malignancy, 44 (57.9%) had an indwelling central vein (CV) catheter, 8 (10.5%) had concomitant pulmonary embolization (PE), and 33 (43.3%) were symptomatic. Regarding the thrombus site, the right internal jugular vein was the most common, with 30 cases (35.3%). As regards the treatment method, 53 patients (69.7%) received oral anticoagulants. In 2015, when direct oral anticoagulants (DOACs) was covered by insurance, there were 44 UEDVT cases, of which 34 (77.3%) received DOACs. Outcomes at a mean observation period of 37.5±41.5 months included 40 deaths (52.6%) with a mean survival of 16.3±21.3 months. The most common cause of death was malignancy, with 33 cases (82.5%). Conclusion: In the background of UEDVT, the combination of indwelling CV catheter placement and malignancy was frequently observed. While the risk of recurrence or PE complications is low, the prognosis of UEDVT complicated by malignancy is extremely poor.

Real-Time Assessment of Tissue Oxygen Saturation Using a Novel Oximeter During Revascularization for Acute Limb Ischemia: A Case Report.

Emergency surgery was performed to treat acute lower limb ischemia caused by heart thromboembolism and concomitant popliteal artery aneurysm. Using a near-infrared spectroscopy oximeter, regional tissue oxygen saturation (rSO2) was monitored to assess the tissue perfusion pre-, intra-, and postoperatively. rSO2 values did not increase sufficiently following thromboembolectomy of the superficial femoral artery, but they dramatically recovered after additional popliteal-anterior tibial bypass surgery. The affected limb was successfully salvaged. rSO2 monitoring was easily measured intraoperatively, which might be beneficial in evaluating tissue perfusion in patients with acute limb ischemia.

Pre-Operative Four Dimensional Flow Sensitive Magnetic Resonance Imaging Assessment of Aortic Side Branches as a Method to Predict Risk of Type II Endoleak Resulting in Sac Enlargement After EVAR.

OBJECTIVE: To predict sac enlargement with type II endoleak (ELII) before endovascular aneurysm repair (EVAR) using four dimensional flow sensitive magnetic resonance imaging (4D flow MRI). METHODS: A single centre retrospective analysis of prospectively collected data was conducted. Patients with an abdominal aortic aneurysm (AAA) who underwent EVAR between 2013 and 2019 were included. Aortic branches occluded pre-EVAR, and patients with endoleaks other than ELII were excluded. The aortic branch diameter, peak flow velocity (PFVe), and amplitude of the dynamics of flow volume (AFV) were measured in each aortic branch pre-EVAR. Total flow volume per minute (TFV/min), defined as the sum of AFV/min, was calculated in each case. According to computed tomography findings one year post-EVAR, the aortic branches and patients were divided into patent vessel and occluded vessel groups and sac expanding and non-expanding groups. PFVe, AFV/min, and TFV/min were analysed via receiver operating characteristic curve analysis. RESULTS: The patent aortic branches pre-EVAR (69 inferior mesenteric arteries [IMAs]; 249 lumbar arteries [LAs]) of 100 patients were included. Patent IMAs (n = 14) and occluded IMAs (n = 55), patent LAs (n = 23) and occluded LAs (n = 226), and expanding (n = 9) and non-expanding (n = 91) groups were compared, respectively. No statistically significant difference was observed in branch diameters (IMA; patent, 2.5 ± 0.8 mm, occluded, 2.5 ± 0.8 mm, p < .78 and LA; patent, 1.5 ± 0.3 mm, occluded, 1.5 ± 0.4 mm, p < .35). PFVe (IMA; patent, 262.6 mm2/sec, occluded, 183.4 mm2/sec and LA; patent, 142.6 mm2/sec, occluded, 47.7 mm2/sec) and AFV/min (IMA; patent, 8.4 mL, occluded, 5.2 mL and LA; patent, 4.2 mL, occluded, 1.4 mL) were higher in the patent vessel group (p < .050). TFV/min was statistically significantly higher in the expanding group (24.1 mL/min) than in the non-expanding group (7.0 mL/min) (p < .010). CONCLUSION: Pre-EVAR haemodynamic analyses using 4D flow MRI were useful to detect aortic branches responsible for ELII and to predict AAA cases with sac enlargement. This analysis suggests a new strategy for pre-EVAR aortic branch embolisation.

Characteristics and Prognostic Factors of Venous Thromboembolism in Cancer Patients.

Background: Improving the prognosis of patients with malignant tumors is increasing the number of patients who develop venous thromboembolism. We examined the characteristics and prognostic factors of VTE patients with cancer. Methods: We diagnosed 725 VTE patients from April 2005 to March 2018. There were 322 cancer associated patients (CAT) and 403 non-cancer associated patients (nonCAT). We examined characteristics and prognostic factors of VTE in CAT patients. Results: There were 156 women and 166 men in CAT, and 132 women and 271 men in nonCAT. There was no significant difference in the location of proximal portion of thrombus. When locations were divided into left leg, right leg, and bilateral legs, bilateral cases were more common in CAT group. Comparing the overall survival after VTE diagnosis in the CAT group, the prognosis was poor in patients with high D-dimer level (≧6 µg/mL) along with cancer metastasis and recurrence. Conclusions: Various VTE factors predict prognosis in CAT patients, and CAT is important in the treatment of cancer patients. (This is secondary publication from Jpn J Phlebol 2020; 31(3): 153-159.).

Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema.

Background: Secondary lymphedema (LE) occurs due to the disruption of lymphatic circulation. Lymphatic fluid accumulation in subcutaneous tissues induces adipocyte proliferation. Obesity is an important risk factor for the occurrence and deterioration of LE. Although the relationship between LE and subcutaneous adipose tissue increase has been reported clinically, their pathophysiological relationship remains unknown. Thus, we aimed to verify whether subcutaneous adipose tissue increase is involved in the pathophysiology of secondary LE. Methods and Results: The hindlimb model of secondary LE was created using male Sprague-Dawley rats (control and LE groups; n = 5 each). Skin samples were obtained on postoperative day 168. Histological examination and quantitative real-time polymerase chain reaction analysis of inflammatory adipokines, tumor necrosis factor-alpha (Tnf-α), C-C chemokine ligand 2 (Ccl2), and interleukin-6 (Il-6) were performed. Limb volume and subcutaneous adipose tissues significantly increased in the LE group compared with those in the control. Macrophages aggregated in the augmented adipose tissues, around the adipocytes, and formed crown-like structures (CLSs). The number of CLSs significantly increased in the LE group. These macrophages expressed transforming growth factor-beta 1 (TGF-ß1). Inflammatory adipokine secretion was not observed. Although Il-6 expression increased in the LE group, IL-6 was expressed in subcutaneous myofibroblasts but not in subcutaneous adipocytes. Conclusion: As TGF-ß1 derived from subcutaneous myofibroblasts is involved in skin fibrosis during LE, TGF-ß1 derived from adipose tissues may also play a similar role. Drug treatment for subcutaneous adipose tissue reduction may improve the skin condition in secondary LE and may be a new therapeutic strategy.

Real-time assessment of tissue oxygen saturation during endovascular therapy for chronic limb threatening ischemia using a novel oximeter.

In the present study, we have introduced a novel real-time, near-infrared spectroscopy oximeter, the TOE-20 (Astem, Co, Ltd, Kawasaki, Japan), which can simultaneously measure the regional tissue oxygen saturation (rSO2) in the skin and subcutaneous tissue at three angiosomes of the foot. Seven patients with chronic limb threatening ischemia who had undergone successful revascularization of the superficial femoral artery were included. The analysis revealed a significant correlation between the rSO2 and skin perfusion pressure. After revascularization, the rSO2 and skin perfusion pressure had both increased at the three regions, although the increase at the plantar foot was insignificant. These results indicate that the TOE-20 can be successfully used to monitor the rSO2 during endovascular treatment.

Differences in Vasa Vasorum Distribution in Human Aortic Aneurysms and Atheromas.

The pathophysiological difference between aortic atheromas and aneurysms is unknown. We focused on the vasa vasorum (VV), which play a critical role in maintaining aortic homeostasis and are also involved in vascular diseases. We investigated the differences in VV between the atheromas and aneurysms. Human abdominal aortic samples were obtained from patients with abdominal aortic aneurysm during surgery or autopsy cases. Autopsy cases were divided into 2 groups according to atheromas. The VV were evaluated using immunohistochemical staining for von Willebrand factor. Intimal VV increased in both the atheroma and aneurysm groups, medial VV increased, and adventitial VV decreased only in the aneurysm group. We also observed that the medial VV were connected to the adventitial VV in the atheroma group and to intimal VV in the aneurysm group. We suggest the outside-in VV or inside-out VV theories. Atheroma induces hypoxia of aortic walls, and angiogenic factors might induce an increase of intimal VV derived from adventitial VV (outside-in VV). However, adventitial VV decrease induces hypoxia of aortic walls, and angiogenic factors might induce an increase of intimal VV derived from aortic lumen (inside-out VV). These differences of VV may contribute in elucidating the pathophysiology of aortic diseases.

A phase III, multicenter, single-arm study to assess the utility of indocyanine green fluorescent lymphography in the treatment of secondary lymphedema.

OBJECTIVE: Indocyanine green (ICG) fluorescent lymphography might be useful for assessing patients undergoing lymphatic surgery for secondary lymphedema. The present clinical trial aimed to confirm whether ICG fluorescent lymphography would be useful in evaluating lymphedema, identifying lymphatic vessels suitable for anastomosis, and confirming patency of lymphaticovenular anastomosis in patients with secondary lymphedema. METHODS: The present phase III, multicenter, single-arm, open-label, clinical trial (HAMAMATSU-ICG study) investigated the accuracy of lymphedema diagnosis via ICG fluorescent lymphography compared with lymphoscintigraphy, rate of identification of lymphatic vessels at the incision site, and efficacy for confirming patency of lymphaticovenular anastomosis. The external diameter of the identified lymphatic vessels and the distance from the skin surface to the lymphatic vessels using preoperative ICG fluorescent lymphography were measured intraoperatively under surgical microscopy. RESULTS: When the clinical decision for surgery at each research site was made, the standard diagnosis of lymphedema was considered correct. For the 26 upper extremities, a central judgment committee who was unaware of the clinical presentation confirmed the imaging diagnosis was accurate for 100.0% of cases, whether the assessments had been performed via lymphoscintigraphy or ICG lymphography. In contrast, for the 88 lower extremities, the accuracy of the diagnosis compared with the diagnosis by the central judgment committee was 70.5% and 88.2% for lymphoscintigraphy and ICG lymphography, respectively. The external diameter of the identified lymphatic vessels was significantly greater in the lower extremities than in the upper extremities (0.54 ± 0.21 mm vs 0.42 ± 0.14 mm; P < .0001). Also, the distance from the skin surface to the lymphatic vessels was significantly longer in the lower extremities than in the upper extremities (5.8 ± 3.5 mm vs 4.4 ± 2.6 mm; P = .01). For 263 skin incisions, with the site placement determined using ICG fluorescent lymphography, the rate of identification of lymphatics vessels suitable for anastomosis was 97.7% (95% confidence interval, 95.1%-99.2%). A total of 267 lymphaticovenular anastomoses were performed. ICG fluorescent lymphography was judged as "useful" for confirming patency after the anastomosis in 95.1% of the cases. CONCLUSIONS: ICG fluorescent lymphography could be useful for improving the treatment of patients with secondary lymphedema from the outpatient setting to surgery.

Kidney transplantation from a living donor with renal artery fibromuscular dysplasia: A case report on arterial grafting of the donor renal artery.

INTRODUCTION: Renal artery fibromuscular dysplasia is generally considered a contraindication of kidney transplantation, since fibromuscular dysplasia occasionally induces hypertension or renal insufficiency in the recipient and/or donor. To date, limited information remains available with respect to whether kidneys with renal arterial fibromuscular dysplasia can be successfully transplanted. CASE PRESENTATION: A 53-year-old potential donor was diagnosed with fibromuscular dysplasia of the right renal artery. Laparoscopic right nephrectomy was performed, and the affected portion was resected and reconstructed using the harvested internal iliac artery. Transplantation was successful and the serum creatinine level was <2 mg/dL for 3 years after surgery. CONCLUSION: If reconstruction of the diseased artery could be safely performed, transplantation using a kidney from a donor with renal artery fibromuscular dysplasia may be considered.

HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema.

INTRODUCTION: Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery. METHODS AND ANALYSIS: This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy-one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA. ETHICS AND DISSEMINATION: The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020. TRIAL REGISTRATION NUMBER: jRCT2031190064; Pre-results.

Potential role of transforming growth factor-beta 1/Smad signaling in secondary lymphedema after cancer surgery.

Secondary lymphedema often develops after cancer surgery, and over 250 million patients suffer from this complication. A major symptom of secondary lymphedema is swelling with fibrosis, which lowers the patient's quality of life, even if cancer does not recur. Nonetheless, the pathophysiology of secondary lymphedema remains unclear, with therapeutic approaches limited to physical or surgical therapy. There is no effective pharmacological therapy for secondary lymphedema. Notably, the lack of animal models that accurately mimic human secondary lymphedema has hindered pathophysiological investigations of the disease. Here, we developed a novel rat hindlimb model of secondary lymphedema and showed that our rat model mimics human secondary lymphedema from early to late stages in terms of cell proliferation, lymphatic fluid accumulation, and skin fibrosis. Using our animal model, we investigated the disease progression and found that transforming growth factor-beta 1 (TGFB1) was produced by macrophages in the acute phase and by fibroblasts in the chronic phase of the disease. TGFB1 promoted the transition of fibroblasts into myofibroblasts and accelerated collagen synthesis, resulting in fibrosis, which further indicates that myofibroblasts and TGFB1/Smad signaling play key roles in fibrotic diseases. Furthermore, the presence of myofibroblasts in skin samples from lymphedema patients after cancer surgery emphasizes the role of these cells in promoting fibrosis. Suppression of myofibroblast-dependent TGFB1 production may therefore represent an effective pharmacological treatment for inhibiting skin fibrosis in human secondary lymphedema after cancer surgery.

Target region oxygenation-based endovascular treatment in a chronic limb-threatening ischemia patient with multifocal arterial diseases.

Patients with chronic limb-threatening ischemia often have multiple segmental diseases requiring revascularization. However, there is no defined milestone to indicate sufficient endovascular treatment (EVT). Using multiple near-infrared spectroscopic oximeters, we intraoperatively monitored regional tissue oxygen saturation (rSO2) to perform target region oxygenation-based EVT for a patient with chronic limb-threatening ischemia. Stent placement at the superficial femoral artery and angioplasty of the tibioperoneal trunk enabled rSO2 in the target ischemic regions (dorsal foot and heel) to be >50% for ulcer healing. We herein describe target region oxygenation-based EVT with rSO2 monitoring as an effective strategy for performing the minimum requisite procedures.

Development of a Noninvasive Skin Evaluation Method for Lower Limb Lymphedema.

Background: The skin's condition is altered in lymphedema patients, and evaluating this change is important. Some noninvasive methods for evaluating skin condition have been reported, especially in upper limb lymphedema. However, evaluating the skin in lower limb lymphedema remains challenging and is often limited to palpation. We aimed to develop a noninvasive skin evaluation method for lower limb lymphedema patients. Methods and Results: Twenty-five lower limb lymphedema patients were included. Skin induration and elasticity were measured using Indentometer® IDM 400 and Cutometer® MPA580. The relationship between the properties of skin from the healthy forearm and thigh, those of the affected thigh, and age was analyzed. Predicted skin induration age (IA) and elasticity age (EA) were calculated from the forearm, whereas actual values were calculated from the thigh, and the differences (ΔIA and ΔEA) were assessed. Patients were classified according to the International Society of Lymphology clinical staging system, and the differences in ΔIA and ΔEA were analyzed among the three groups (healthy, stage I/IIa, and stage IIb/III). Skin biopsy was performed in five unilateral lower limb lymphedema patients, and the dermal elastic fiber area was determined using microscopy with Elastica van Gieson staining. ΔEA significantly increased with disease progression, but ΔIA did not change significantly. Microscopy revealed elastic fiber filamentous changes, with decreased elastic fiber areas in lymphedema-affected skin. Conclusion: To our knowledge, this is the first report to evaluate lower limb skin elasticity in lymphedema quantitatively and noninvasively. ΔEA is useful for evaluating skin condition progression in lymphedema patients.

Flow dynamics of type II endoleaks can determine sac expansion after endovascular aneurysm repair using four-dimensional flow-sensitive magnetic resonance imaging analysis.

OBJECTIVE: The objective of this study was to investigate the hemodynamic parameters of type II endoleaks (T2ELs) to predict sac expansion using four-dimensional flow-sensitive magnetic resonance imaging (4D-flow MRI) analysis. METHODS: Patients who underwent endovascular aneurysm repair (EVAR) and were diagnosed with a T2EL were included in the study. Using 4D-flow MRI at 7 days, the peak flow velocity and amplitude of dynamics of blood flow per minute were measured in each T2EL vessel. The peak flow velocity was defined as the maximum of the absolute value of the blood flow velocity. The amplitude of dynamics of blood flow in the tributary arteries was defined as the sum of the absolute values of the inflow and outflow volume in each vessel. The amplitude of dynamics of blood flow in the tributary arteries per sac was calculated in each sac. The aneurysm sac diameter was measured by computed tomography (CT) at 1 year. The patients were divided into two groups according to the presence or absence of sac expansion. RESULTS: Of 155 patients who underwent EVAR, both CT angiography and 4D-flow MRI were performed in 107 patients at 7 days after EVAR. Among them, 39 (36.4%) were found to have a T2EL, of whom 28 were re-evaluated with CT angiography and 4D-flow at 1 year; 7 patients had expanding sacs (expanding group), whereas 21 had nonexpanding sacs (not-expanding group). At 7 days, 28 patients had 80 T2EL vessels detected by 4D-flow MRI, of which 39 vessels (48.8%) had stopped flowing at 1 year (transient vessels); 41 vessels (51.3%) had sustained flow (persistent vessels). The persistent vessels had significantly larger peak flow velocity and amplitude of dynamics of blood flow. The comprehensive analysis of T2EL vessels per sac identified that the amplitude of dynamics of blood flow in the tributary arteries per sac was significantly higher in the expanding group than in the not-expanding group. A receiver operating characteristic curve analysis revealed that the sensitivity and specificity of sac enlargement at a cutoff value of 3750 mm3/min were 85.7% and 76.2%, respectively. CONCLUSIONS: The fate of aneurysm sacs with T2ELs after EVAR has remained difficult to predict. A comprehensive analysis of concurrent multiple T2EL vessels using 4D-flow MRI analysis may enable prediction of the sac expansion after EVAR.

Axillo-Axillary Artery Bypass With Coil Embolization of the Innominate Artery for a Traumatic Innominate Artery Aneurysm: A Case Report.

BACKGROUND: Innominate artery aneurysm (IAA) is a rare cervical artery aneurysm. Although atherosclerosis is its most common cause, IAAs due to cervical injury are often reported. Operative indications for IAAs include rupture or symptomatic aneurysm, saccular aneurysm, aneurysm with a diameter of 3 cm or greater, and aneurysmal change of the origin of the innominate artery. Although the ligature of the innominate artery or open surgical repair is well described, the usefulness of endovascular repair has also recently been reported. Herein, we report a case of traumatic IAA with infection in the cervical region after tracheostomy. CASE PRESENTATION: A 40-year-old man with cholecystolithiasis planned to undergo laparoscopic cholecystectomy at another hospital. Urgent tracheostomy was performed because of laryngeal edema at the induction of general anesthesia. Enhanced computed tomography angiography 1 week after the tracheostomy revealed a saccular IAA. The patient was deemed to be at high risk for aneurysm rupture and was referred to our hospital. Preoperative Matas test, Allcock test, and innominate arterial stump pressure measurement were performed to assess the cerebral blood flow and ischemic tolerance of the brain. These examinations showed the patency of the circle of Willis. An axillo-axillary artery bypass with coil embolization of the innominate artery was performed to avoid postoperative vascular graft infection. No postoperative complications such as infection or cerebral infarction occurred. Magnetic resonance imaging angiography performed 6 months after surgical treatment showed that the aneurysm had disappeared, and patency of the bypass graft was present. There were no postoperative complications, such as neurological deficits or graft infection, at more than 5 years after surgery. CONCLUSIONS: We report a successfully treated case of IAA after tracheostomy. Axillo-axillary artery bypass with coil embolization of the innominate artery is an effective treatment of IAA with cervical infection.

Insufficient Lymph Drainage Causes Abnormal Lipid Accumulation and Vein Wall Degeneration.

Objective: Previously, we analyzed human varicose veins (VV) using imaging mass spectrometry (IMS) and detected the abnormal accumulation of lipid molecules in the walls of VV, possibly due to insufficient lipid drainage by the lymphatic vessels. In this study, we created an animal model of lymphatic insufficiency to investigate the effects of insufficient lymph drainage on vein walls. Methods: In rats, the lymphatic collecting vessels surrounding the femoral vein were ligated on one side (the model tissue), which caused the local retention of lymphatic fluid in the perivascular tissue. The equivalent contralateral tissue was used as a control. A histological study of the femoral vein and the surrounding perivascular tissue was conducted. IMS was used to analyze the distribution of lipid molecules in the perivascular tissue. Results: Fourteen days after the procedure, the lymphatic vessels in the model tissue were significantly dilated. Furthermore, IMS revealed that the composition of the lipid molecules in the perivascular regions of the model tissue had altered. Compared with the control tissue, the model tissue exhibited marked perivascular accumulation of lysophosphatidylcholine (1-acyl 16:0), phosphatidylcholine (16:0/20:4), and triglycerides (52:2). Interestingly, the walls of the femoral veins running through the model tissue were 3.4-fold thicker than those of the femoral veins running through the control tissue. The number of tumor necrosis factor α-positive adipocytes was increased in the perivascular regions of the model tissue. Conclusion: The findings of this study indicated that the accumulation of lymphatic fluid due to insufficient lymph drainage changes the structure of vein walls, and such changes might be associated with chronic venous insufficiency. (This is a translation of Jpn J Phlebol 2015; 26: 227-235.).

Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a vascular disease involving the gradual dilation of the abdominal aorta. It has been reported that development of AAA is associated with inflammation of the vascular wall; however, the mechanism of AAA rupture is not fully understood. In this study, we investigated the mechanism underlying AAA rupture using a hypoperfusion-induced animal model. We found that the administration of triolein increased the AAA rupture rate in the animal model and that the number of adipocytes was increased in ruptured vascular walls compared to non-ruptured walls. In the ruptured group, macrophage infiltration and the protein levels of matrix metalloproteinases 2 and 9 were increased in the areas around adipocytes, while collagen-positive areas were decreased in the areas with adipocytes compared to those without adipocytes. The administration of fish oil, which suppresses adipocyte hypertrophy, decreased the number and size of adipocytes, as well as decreased the risk of AAA rupture ratio by 0.23 compared to the triolein administered group. In human AAA samples, the amount of triglyceride in the adventitia was correlated with the diameter of the AAA. These results suggest that AAA rupture is related to the abnormal appearance of adipocytes in the vascular wall.

Characteristic Distribution Pattern of Lysophosphatidylcholine in Fibromuscular Dysplasia-Associated Visceral Artery Aneurysms Compared with Atherosclerotic Visceral Artery Aneurysms.

AIM: Asymptomatic visceral artery aneurysms (VAAs) have increasingly been found, with most being either atherosclerotic VAAs or fibromuscular dysplasia (FMD)-associated VAAs. However, little is known about the pathogenesis of both diseases. We aimed to identify the differences in the distribution pattern of lipid molecules between atherosclerotic VAAs and FMD-associated VAAs. METHODS: We conducted a histological study of VAAs using imaging mass spectrometry (IMS) to assess the accumulation of lipid molecules in both the aneurysmal sac and the adjacent arteries without aneurysmal changes in 17 VAA samples, which were resected during the surgery. RESULTS: IMS revealed characteristic distributions of cholesterol ester in intima and media in the atherosclerotic VAAs, which was hardly detected in FMD-associated VAAs. However, lysophosphatidylcholine (lysoPC), a proinflammatory and proapoptotic lipid mediator, was accumulated in the medial ridge of the adventitia of FMD-associated in the aneurysmal sac, and it was also diffusely accumulated in the adjacent arteries. In contrast, lysoPC was accumulated in the area of intimal hyperplasia in atherosclerotic VAAs and the adjacent arteries. CONCLUSION: The distribution patterns of lipid molecules were different between the FMD-associated and atherosclerotic VAAs. The diffuse accumulation of lysoPCs in the visceral arteries may be a predisposition for the formation of FMD-associated VAAs.