Clinical outcomes of acute myocardial infarction arising from non-lipid-rich plaque determined by NIRS-IVUS.

Acute myocardial infarction (AMI) can rarely arise from non-lipid-rich coronary plaques. This study sought to compare the clinical outcomes after percutaneous coronary intervention (PCI) between AMI showing maximum lipid-core burden index in 4 mm (maxLCBI4mm) < 400 and ≥ 400 in the infarct-related lesions assessed by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We investigated 426 AMI patients who underwent NIRS-IVUS in the infarct-related lesions before PCI. Major adverse cardiovascular events (MACE) were defined as the composite of cardiac death, non-fatal MI, clinically driven target lesion revascularization (TLR), clinically driven non-TLR, and congestive heart failure requiring hospitalization. 107 (25%) patients had infarct-related lesions of maxLCBI4mm < 400, and 319 (75%) patients had those of maxLCBI4mm ≥ 400. The maxLCBI4mm < 400 group had a younger median age at onset (68 years [IQR: 57-78 years] vs. 73 years [IQR: 64-80 years], P = 0.007), less frequent multivessel disease (39% vs. 51%, P = 0.029), less frequent TIMI flow grade 0 or 1 before PCI (62% vs. 75%, P = 0.007), and less frequent no-reflow immediately after PCI (5% vs. 11%, P = 0.039). During a median follow-up period of 31 months [IQR: 19-48 months], the frequency of MACE was significantly lower in the maxLCBI4mm < 400 group compared with the maxLCBI4mm ≥ 400 group (4.7% vs. 17.2%, P = 0.001). MaxLCBI4mm < 400 was an independent predictor of MACE-free survival at multivariable analysis (hazard ratio: 0.36 [confidence interval: 0.13-0.98], P = 0.046). MaxLCBI4mm < 400 measured by NIRS in the infract-related lesions before PCI was associated with better long-term clinical outcomes in AMI patients.

Maternal high-fat diet promotes calcified atherosclerotic plaque formation in adult offspring by enhancing transformation of VSMCs to osteochondrocytic-like phenotype.

Aim: Maternal high-fat diet (HFD) is associated with the development of cardiovascular disease (CVD) in adult offspring. Atherosclerotic vascular calcification is well documented in patients with CVD. We examined the effect of maternal HFD on calcified plaque formation. Methods and results: Seven-week-old female apo-E-/- mice (C57BL6/J) were nourished either an HFD or a normal diet (ND) a week before mating, and during gestation and lactation. Offspring of both the groups were fed a high-cholesterol diet (HCD) from 8 weeks of age. Osteogenic activity of the thoracic aorta, assessed using an ex vivo imaging system, was significantly increased after 3 months of HCD in male offspring of HFD-fed dams (O-HFD) as compared with those of ND-fed dams (O-ND). Alizarin-red-positive area in the aortic root was significantly increased after 6 months of HCD in male O-HFD as compared to that of O-ND. Plaque size and Oil Red O-positive staining were comparable between the two groups. Primary cultured vascular smooth muscle cells (VSMCs) of the thoracic aorta were treated with phosphate and interleukinL-1ß (IL-1ß) to transform them into an osteochondrocytic-like phenotype. Intracellular calcium content and alkaline phosphatase activity were markedly higher in the VSMCs of O-HFD than in O-ND. IL-1ß concentration in the supernatant of bone marrow-derived macrophages was markedly higher in O-HFD than in O-ND. Conclusion: Our findings indicate that maternal HFD accelerates the expansion of atherogenic calcification independent of plaque progression. In vitro phosphate- and IL-1ß-induced osteochondrocytic transformation of VSMCs was augmented in O-HFD. Inhibition of VSMCs, skewing toward osteochondrocytic-like cells, might be a potential therapeutic strategy for preventing maternal HFD-associated CVD development.

Repeated Social Defeat Enhances CaCl2-Induced Abdominal Aortic Aneurysm Expansion by Inhibiting the Early Fibrotic Response via the MAPK-MKP-1 Pathway.

Depression is an independent risk factor for cardiovascular disease and is significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We investigated the effect of repeated social defeat (RSD) on AAA development. Eight-week-old male wild-type mice were exposed to RSD by being housed with larger CD-1 mice in a shared cage. They were subjected to vigorous physical contact. After the confirmation of depressive-like behavior, calcium chloride was applied to the infrarenal aorta of the mice. At one week, AAA development was comparable between the defeated and control mice, without any differences being observed in the accumulated macrophages or in the matrix metalloproteinase activity. At two weeks, the maximum diameter and circumference of the aneurysm were significantly increased in the defeated mice, and a significant decrease in periaortic fibrosis was also observed. Consistently, the phosphorylation of the extracellular signal-regulated kinase and the incorporation of 5-bromo-2'-deoxyuridine in the primarily cultured aortic vascular smooth muscle cells were significantly reduced in the defeated mice, which was accompanied by a substantial increase in mitogen-activated protein kinase phosphatase-1 (MKP-1). The MKP-1 mRNA and protein expression levels during AAA were much higher in the defeated mice than they were in the control mice. Our findings demonstrate that RSD enhances AAA development by suppressing periaortic fibrosis after an acute inflammatory response and imply novel mechanisms that are associated with depression-related AAA development.

The effectiveness of scoring balloon angioplasty in the treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an effective treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of this study is to evaluate the therapeutic effect and safety of the non-slip element percutaneous transluminal angioplasty (NSE PTA) scoring balloons in BPA. METHODS: 108 pulmonary artery branches in 14 CTEPH patients who underwent BPA using NSE PTA scoring balloon (the NSE PTA group) or plain balloon (the POBA group) and pressure gradient evaluation were analyzed. We compared the improvement of the pressure ratios after BPA (Δ Pressure ratio) of both groups. RESULTS: There was no significant difference in the Δ Pressure ratios of the two groups (0.241 ± 0.196 POBA, 0.259 ± 0.177 NSE PTA, p = 0.63). No complications occurred in the NSE PTA group, while 3 episodes of hemoptysis were seen in the POBA group. This, however, was not found to be significant (p = 0.27). In the cases where balloon-to-vessel ratio exceeded 1.0 (n = 35), multivariate analysis showed that the use of NSE PTA scoring balloon and pressure ratio before BPA were significantly correlated with Δ Pressure ratio (ß coefficient: 0.047, 95% CI: 0.0016 to 0.093, p = 0.043 and ß coefficient: -0.60, 95% CI: -0.78 to -0.42, p < 0.01, respectively). CONCLUSIONS: Although NSE PTA scoring balloon was safe, there was no significant pressure gradient improvement with NSE PTA scoring balloon compared to conventional BPA. Nevertheless, the NSE PTA scoring balloon showed effective blood-flow improvement in the case of large balloon-to-vessel ratio.

Repeated Social Defeat Exaggerates Fibrin-Rich Clot Formation by Enhancing Neutrophil Extracellular Trap Formation via Platelet-Neutrophil Interactions.

Depression is an independent risk factor for cardiovascular disease (CVD). We have previously shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular trap (NET) formation. In this study, we investigated the impact of RSD on arterial thrombosis. Eight-week-old male wild-type mice (C57BL/6J) were exposed to RSD by housing with larger CD-1 mice in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. After confirming depression-like behaviors, mice underwent FeCl3-induced carotid arterial injury and were analyzed after 3 h. Although the volume of thrombi was comparable between the two groups, fibrin(ogen)-positive areas were significantly increased in defeated mice, in which Ly-6G-positive cells were appreciably co-localized with Cit-H3-positive staining. Treatment with DNase I completely diminished exaggerated fibrin-rich clot formation in defeated mice. Flow cytometric analysis showed that neutrophil CD11b expression before FeCl3 application was significantly higher in defeated mice than in control mice. In vitro NET formation induced by activated platelets was significantly augmented in defeated mice, which was substantially inhibited by anti-CD11b antibody treatment. Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NET formation, suggesting that NET can be a new therapeutic target in depression-related CVD.

Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation.

Maternal high-fat diet (HFD) modulates vascular remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) development. Female wild-type mice were fed an HFD or normal diet (ND). AAA was induced in eight-week-old pups using calcium chloride. Male offspring of HFD-fed dams (O-HFD) showed a significant enlargement in AAA compared with the offspring of ND-fed dams (O-ND). Positive-staining cells for tartrate-resistant acid phosphate (TRAP) and matrix metalloproteinase (MMP) activity were significantly increased in O-HFD. The pharmacological inhibition of osteoclastogenesis abolished the exaggerated AAA development in O-HFD. The in vitro tumor necrosis factor-α-induced osteoclast-like differentiation of bone marrow-derived macrophages showed a higher number of TRAP-positive cells and osteoclast-specific gene expressions in O-HFD. Consistent with an increased expression of nuclear factor of activated T cells 1 (NFATc1) in O-HFD, the nuclear protein expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor, were much lower, with significantly increased H3K27me3 marks at the promoter region. The enhancer of zeste homolog 2 inhibitor treatment restored IRF8 expression, resulting in no difference in NFATc1 and TRAP expressions between the two groups. Our findings demonstrate that maternal HFD augments AAA expansion, accompanied by exaggerated osteoclast-like macrophage accumulation, suggesting the possibility of macrophage skewing via epigenetic reprogramming.

Favorable changes of left ventricular function in the circumferential direction following transcatheter atrial septal defect closure: a strain imaging study.

To clarify the impact on left ventricular (LV) function of percutaneous atrial septal defect (ASD) closure in adult patients. Echocardiograms of 46 patients (52 ± 18 years) who underwent ASD closure with a significant left-to-right shunt obtained before and 1 month after the procedure were retrospectively analyzed. Functional parameters were obtained by 2-dimensional speckle-tracking imaging. Global longitudinal strain and strain rate at early diastole (SRe) was calculated from the three standard apical views, while circumferential and radial parameters were calculated from basal, middle, and apical LV short-axis views. Along with a diminished right ventricular (RV) volume, the LV volume and ejection fraction increased (end-diastolic volume: 61 ± 12 to 76 ± 15 mL, p < 0.001; and 63% ± 4 to 64% ± 4% p = 0.03; respectively). Both global strain and SRe was augmented only in the circumferential direction (- 16.2% ± 2.9% to - 19.8% ± 2.8%; and 1.07 ± 0.29 to 1.34 ± 0.28 s-1, both p < 0.001). Augmentation of circumferential SRe correlated with both the changes in and the pre-procedural value of diastolic LV eccentricity index (r = - 0.57, p < 0.001; and r = 0.37, p = 0.01; respectively), a morphological parameter of RV volume overload. Following ASD closure in adults, both LV systolic and diastolic function could favorably change in the circumferential direction, and the degree of diastolic functional change is associated with RV volume overload, i.e., severity of ventricular interdependence.

Knowledge, perception, and level of confidence regarding COVID-19 care among healthcare workers involved in cardiovascular medicine: a web-based cross-sectional survey in Japan.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has a significant impact on daily practice in cardiovascular medicine. The preparedness of healthcare workers (HCWs) can affect the spread of infection and the maintenance of the healthcare system. This study aimed to investigate the knowledge, perception, and level of confidence regarding COVID-19 care among HCWs involved in cardiovascular medicine. METHODS: A cross-sectional, web-based study about COVID-19 was performed between April 22 and May 7, 2020, among 311 HCWs in cardiovascular departments. The demographic information, COVID-19-related knowledge, and perception and level of confidence toward COVID-19 care were assessed. RESULTS: The median age of the participants was 38 years, and 215 (69.8%) were male. There were 134 (43.1%) physicians and 177 (56.9%) non-physician HCWs. The HCWs, especially non-physician HCWs, had insufficient knowledge about infection-prevention measures for COVID-19, such as how to isolate patients with COVID-19, how to use personal protective equipment, and how to prevent infection during aerosol-generating procedures. Most HCWs showed a low level of confidence toward COVID-19 care, and such poor confidence was associated with the lack of knowledge on optimal infection-prevention measures. CONCLUSIONS: This survey revealed the lack of knowledge about adequate infection-prevention measures for COVID-19. More attention should be paid to the preparedness of HCWs, and educating and supporting HCWs involved in cardiovascular medicine is an urgent need.

Immunoglobulin G4-Related Coronary Artery Aneurysm-Associated Stent Migration.

A 65-year-old woman with immunoglobulin G4-related disease (IgG4-RD), which was managed with a corticosteroid, underwent percutaneous coronary stent implantation in the left anterior descending artery as a result of angina pectoris. After 9 months, coronary angiography revealed stent migration and occlusion caused by progression of a coronary aneurysm potentially associated with IgG4-RD. (Level of Difficulty: Advanced.).

Acute coronary syndrome with large thrombus successfully managed with no-stenting revascularization based on intravascular imaging in a patient with hyperhomocysteinemia: a case report.

BACKGROUND: Hyperhomocysteinemia is caused by genetic and environmental factors, which can result in systemic arteriosclerosis and arteriovenous thrombosis including acute coronary syndrome. Thrombus burden in patients with acute coronary syndrome and hyperhomocysteinemia might involve the culprit lesion as compared with those without any coagulopathy. The primary percutaneous coronary intervention with stent implantation had been established as the treatment strategy for patients with acute coronary syndrome. However, in patients with acute coronary syndrome with high thrombus burden or uncontrolled coagulopathy, stent implantation might lead to slow-flow phenomenon or stent thrombosis. Therefore, the treatment strategy in these patients was not established. CASE PRESENTATION: A 49-year-old Japanese man with history of splenic infarction of unknown cause had continued anticoagulant therapy since its diagnosis, but stopped taking the medication several months ago. He presented with sudden-onset chest dorsalgia. Contrast computed tomography showed a small pulmonary embolism and his troponin I level was elevated on initial laboratory test. Coronary angiography revealed a contrast defect caused by a large thrombus from the proximal to mid portion of the left anterior descending artery. Near-infrared spectroscopy-intravascular ultrasonography showed a large amount of thrombus without lipid plaque. Therefore, revascularization was performed using a thrombus-aspiration catheter and intracoronary thrombolysis. In addition, , hyperhomocysteinemia and a deep vein thrombosis occurred. He was diagnosed with acute coronary syndrome complicated with pulmonary embolism and deep vein thrombosis simultaneously induced by hyperhomocysteinemia. After 1 week of antithrombotic therapy, near-infrared spectroscopy-intravascular ultrasonography and optical coherence tomography revealed a decreased thrombus and no significant residual organic stenosis in the left anterior descending artery. He continued conservative therapy with antithrombotic medications including aspirin and warfarin and had no cardiovascular events after discharge. Follow-up coronary angiography and optical coherence tomography at 9 months revealed complete disappearance of the thrombus and no severe stenosis. CONCLUSIONS: Hyperhomocysteinemia should be considered as a cause of arterial vein thrombosis of unknown cause. The antithrombotic therapy and percutaneous revascularization without stenting based on intravascular imaging might be a safe and effective treatment option in patients with acute coronary syndrome complicated with hyperhomocysteinemia.

Two effective cases of additional pedal artery angioplasty for severe lower limb ischemia following acute thrombotic artery occlusion with hypercoagulable state diseases.

BACKGROUND: Acute limb ischemia (ALI) and critical limb ischemia (CLI) following ALI are life-threatening diseases. The rare potential causes of ALI include hypercoagulable state diseases, such as antiphospholipid syndrome (APS) and essential thrombocythemia (ET). Hypercoagulability often make revascularization for arterial occlusion, especially associated with infrapopliteal lesions, difficult. This is because the vessels have poor run-off, and elevated peripheral vascular resistance associated with microcirculation failure, due to a high thrombus burden. There is no established treatment for this issue. CASE PRESENTATION: A 45 years-old and a 56 years-old male suffered from thrombotic arterial occlusion as a first manifestation of APS and ET, respectively. Combination therapy with aggressive anti-thrombotic therapy and revascularization, such as endovascular therapy and surgical thrombectomy based on the angiosome concept, was performed. However, the high thrombus burden caused a poor pedal outflow, and significant limb ischemia remained. Additional pedal artery angioplasty was performed to improve residual limb ischemia in each case and provided sufficient blood flow to the foot. CONCLUSION: The pedal artery angioplasty for thrombotic pedal artery occlusion cases, associated with hypercoagulable state diseases, seems to be a treatment option for relieving residual limb ischemia.

Social Stress Increases Vulnerability to High-Fat Diet-Induced Insulin Resistance by Enhancing Neutrophil Elastase Activity in Adipose Tissue.

Social stress (SS) has been linked to the development of cardiovascular disease (CVD), which is closely associated with insulin resistance (IR); however, the causal effect of SS on IR remains unclear. The 8-week-old male C57BL/6 mice were exposed to SS by housing with a larger CD-1 mouse in a shared home cage without physical contact for 10 consecutive days followed by high-fat diet (HFD) feeding. Control mice were housed in the same cage without a CD-1 mouse. After 6 weeks of HFD, insulin sensitivity was significantly impaired in stressed mice. While the percentage of classically activated macrophages in epididymal white adipose tissue (eWAT) was equivalent between the two groups, the percentage of lymphocyte antigen 6 complex locus G6D (Ly-6G)/neutrophil elastase (NE)-double positive cells markedly increased in stressed mice, accompanied by augmented NE activity assessed by ex vivo eWAT fluorescent imaging. Treatment with an NE inhibitor completely abrogated the insulin sensitivity impairment of stressed mice. In vitro NE release upon stimulation with a formyl peptide receptor 1 agonist was significantly higher in bone marrow neutrophils of stressed mice. Our findings show that SS-exposed mice are susceptible to the development of HFD-induced IR accompanied by augmented NE activity. Modulation of neutrophil function may represent a potential therapeutic target for SS-associated IR.

Maternal high-fat diet exaggerates diet-induced insulin resistance in adult offspring by enhancing inflammasome activation through noncanonical pathway of caspase-11.

OBJECTIVE: Maternal high-fat diet (HFD) has been shown to promote the development of insulin resistance (IR) in adult offspring; however, the underlying mechanisms remain unclear. METHODS: Eight-week-old female wild-type mice (C57BL/6) were fed either an HFD or a normal diet (ND), one week prior to mating, and the diet was continued throughout gestation and lactation. Eight-week-old male offspring of both groups were fed an HFD for 8 weeks. RESULTS: Offspring of HFD-fed dams (O-HFD) exhibited significantly impaired insulin sensitivity compared with the offspring of ND-fed dams (O-ND). The adipocyte size of the eWAT increased significantly in O-HFD and was accompanied by abundant crown-like structures (CLSs), as well as a higher concentration of interleukin 1ß (IL-1ß) in the eWAT. Treatment with an inflammasome inhibitor, MCC950, completely abrogated the enhanced IR in O-HFD. However, ex vivo caspase-1 activity in eWAT revealed no difference between the two groups. In contrast, noncanonical inflammasome activation of caspase-11 was significantly augmented in O-HFD compared with O-ND, suggesting that membrane pore formation, but not cleavage of pro-IL-1ß by caspase-1, is augmented in O-HFD. To examine the membrane pore formation, we performed metabolic activation of bone marrow-derived macrophages (BMDMs). The percentage of pore formation assessed by ethidium bromide staining was significantly higher in BMDMs of O-HFD, accompanied by an enhanced active caspase-11 expression. Consistently, the concentration of IL-1ß in culture supernatants was significantly higher in the BMDMs from O-HFD than those from O-ND. CONCLUSIONS: These findings demonstrate that maternal HFD exaggerates diet-induced IR in adult offspring by enhancing noncanonical caspase-11-mediated inflammasome activation.

Comparative Analysis of the Paclitaxel-Eluting Peripheral Igaki-Tamai Stent and the Drug-Free Igaki-Tamai Stent Using Optical Coherence Tomography and Histological Analysis in a Porcine Iliac Artery Model.

BACKGROUND: The combination of a bioresorbable scaffold and antiproliferative drugs is a promising treatment for peripheral artery disease. The novel paclitaxel-eluting peripheral Igaki-Tamai stent (PTX-ITS) has the same backbone design as the drug-free peripheral Igaki-Tamai stent and a paclitaxel coating. Arterial responses to the PTX-ITS and ITS using optical coherence tomography (OCT) and histological analysis in a porcine iliac artery model were compared.Methods and Results:In total, 6 PTX-ITSs and 6 ITSs implanted in porcine iliac arteries were evaluated. Quantitative measurements of the scaffold, lumen, neointimal areas, and percent area stenosis were performed using OCT at 1 and 3 months. Histological evaluations (PTX-ITS [n=5], ITS [n=4]) were performed following euthanasia at 3 months. Injury, inflammation, endothelialization, and fibrin scores were measured. Baseline angiographic characteristics were similar in both groups. The ITS group showed significantly smaller scaffold areas than the PTX-ITS group at 1 month (18.50±3.62 mm2vs. 23.54±3.64 mm2; P=0.037) and 3 months (15.82±2.57 mm2vs. 21.67±3.57 mm2; P=0.009). Percent area stenosis was significantly lower in the PTX-ITS group at 3 months (28.70±7.24% vs. 40.36±7.07%; P=0.018). Histological evaluations revealed similar low-grade inflammatory reactions for both scaffolds. CONCLUSIONS: PTX-ITSs showed significantly better suppression of late scaffold shrinkage and lower in-scaffold stenosis for up to 3 months. Additionally, PTX-ITSs exhibited high biocompatibility, which is comparable to ITSs.

A newly designed 0.018-in.-compatible inner dilator as a novel option for endovascular therapy with the crossover approach.

This study aimed to investigate the efficacy of guiding sheath delivery with the crossover approach using a newly customized inner dilator for a 0.018-in. guidewire of the Destination® guiding sheath (Terumo Corporation, Tokyo, Japan) (18-system), compared with that of the conventional-type 0.035-in. guidewires with inner dilators (35-system), and to predict failure of guiding sheath delivery. We conducted a prospective multicenter case series study of the contralateral crossover approach using Destination®, to determine whether the 18-system could be a rescue system in cases in which the conventional 35-system failed. To evaluate the efficacy of the 18-system, we created an in vitro aortoiliac bifurcation model by using a silicone vessel. We enrolled 172 cases consecutively. The initial crossover approach with the 35-system failed in 37 cases (21.5%), and a second attempt with the 18-system was successful in all failed cases. The bifurcation angles in the 35-system failure cases were significantly steeper than those in the 35-system success cases. A receiver operating characteristic curve analysis demonstrated that an aortoiliac bifurcation angle of 68° was the optimal cut-off value for predicting failure of the crossover procedure. Data from the analysis using the silicone vessel model suggested that the 18-system provided superior results, especially in aortoiliac bifurcation angles steeper than 60°, consistent with the in vivo findings. The results of the initial use of the 18-system with the crossover approach suggest that it may be superior to the conventional 35-system, especially in cases of steeper aortoiliac bifurcation angles.

Feasibility and Safety of Reverse Catheterization Technique of the Superficial Femoral Artery in Single-Stage Endovascular Treatment of Bilateral Infrainguinal Diseases.

PURPOSE:: We evaluated the feasibility and safety of the reverse catheterization technique of the superficial femoral artery (ReCAT) for single-stage endovascular treatment (EVT) in patients with bilateral infrainguinal diseases. MATERIALS AND METHODS:: We retrospectively evaluated 24 consecutive patients (overall median age: 79 years; male patients: 21 [87.5%]) who underwent EVT for bilateral infrainguinal diseases. The objective of ReCAT was to perform single-stage EVT in patients with bilateral infrainguinal diseases with a one-time unilateral femoral artery puncture. The main outcomes were the incidence of puncture site complications, including major bleeding or hematoma requiring transfusion, pseudoaneurysm, and arteriovenous fistula, and ReCAT procedure-related arterial dissection or perforation, which were assessed by ultrasonography on the day after the procedure. The secondary outcome measures were in-hospital mortality and in-hospital amputation. RESULTS:: Reverse catheterization technique of the superficial femoral artery was successful in 23 (95.8%) of the 24 patients; it failed in 1 patient due to severe calcification and a previously implanted stent in the ipsilateral iliac artery. The median operation time, radiation time, and the volume of contrast media used were 108 (84-142) minutes, 37 (27-55) minutes, and 111 (80-157) mL, respectively. There were no incidences of puncture site complications and arterial dissection related to the ReCAT procedure. One case of vessel perforation in a branch of the ipsilateral superficial femoral artery occurred due to flipped guidewire injury. CONCLUSION:: Reverse catheterization technique of the superficial femoral artery is safe and effective in performing single-stage EVT for bilateral infrainguinal diseases. It might also reduce the number of EVTs and complications due to multiple femoral artery punctures.

Transplantation of periaortic adipose tissue inhibits atherosclerosis in apoE-/- mice by evoking TGF-ß1-mediated anti-inflammatory response in transplanted graft.

Perivascular adipose tissue (PAT) is associated with vascular homeostasis; however, its causal effect on atherosclerosis currently remains undefined. Here, we investigated the effect of experimental PAT transplantation on atherosclerosis. The thoracic periaortic adipose tissue (tPAT) was dissected from 16-week-old wild-type mice and transplanted over the infrarenal aorta of 20-week-old apoE deficient (apoE-/-) mice fed high-cholesterol diet for 3 months. Oil-red O staining after 4 weeks showed a significant 20% decrease in the atherosclerotic lesion of suprarenal aorta compared with that of sham control mice, while that of infrarenal aorta showed no difference between the two groups. TGF-ß1 mRNA expression was significantly higher in grafted tPAT than donor tPAT, accompanied by a significant increase in serum TGF-ß1 concentration, which was inversely correlated with the suprarenal lesion area (r = -0.63, P = 0.012). Treatment with neutralizing TGF-ß antibody abrogated the anti-atherogenic effect of tPAT transplantation. Immunofluorescent analysis of grafted tPAT showed that TGF-ß-positive cells were co-localized with Mac-2-positive cells and this number was significantly increased compared with donor tPAT. There was also marked increase in mRNA expression of alternatively activated macrophages-related genes. Furthermore, the percentage of eosinophils in stromal vascular fraction of donor tPAT was much higher than that in epididymal white adipose tissue, concomitant with the significantly higher protein level of IL-4. IL-4 mRNA expression levels in grafted tPAT were increased in a time-dependent manner after tPAT transplantation. Our findings show that tPAT transplantation inhibits atherosclerosis development by exerting TGF-ß1-mediated anti-inflammatory response, which may involve alternatively activated macrophages.

Augmented neutrophil extracellular traps formation promotes atherosclerosis development in socially defeated apoE-/- mice.

Depression is an independent risk factor of cardiovascular disease (CVD); however, the causal association remains undefined. We exposed mice to repeated social defeat (RSD) to precipitate depressive-like behaviors, and investigated the effects on atherosclerosis. Eight-week-old male apoE-/- mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days and fed a high-cholesterol diet (HCD) for 6 weeks. The social interaction ratio and immobility time showed dramatic social avoidance before and after HCD feeding. Defeated mice showed higher increase in atherosclerotic lesion areas in the aortic root and entire aorta than control mice. Mean blood pressure and lipid profile were equivalent in both groups. While Ly-6G- and Mac3-positive areas in the aortic root were comparable between the groups, citrullinated histone H3 (Cit-H3)- and myeloperoxidase (MPO)-positive areas, markers of neutrophil extracellular traps (NETs), were significantly increased in the defeated mice. Treatment with DNase I completely diminished the exaggerated atherosclerosis. The proportion of peripheral blood polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), but not of inflammatory monocytes, was markedly increased. Moreover, in vitro NETs formation from bone marrow (BM) PMN-MDSC was markedly augmented, accompanied by higher expression of Nox2 gene and reactive oxygen species. Our findings demonstrate that exposure to RSD promotes atherosclerosis by augmenting NETs formation within the plaque. This provides new insight into the underlying mechanism of depression-related CVD.

Adrenergic receptor-mediated activation of FGF-21-adiponectin axis exerts atheroprotective effects in brown adipose tissue-transplanted apoE-/- mice.

Brown adipose tissue (BAT) has been found as an endocrine organ that maintains metabolic homeostasis; however, the effects on atherosclerosis remain undefined. Here, we investigated the effect of experimental BAT transplantation on atherosclerosis. Interscapular BAT was dissected from wild-type mice and transplanted into the visceral cavity of 12-week-old apoE-/- mice. Oil-red O staining of whole aortas after 3 months of a high-cholesterol diet showed a significant decrease in atherosclerotic lesion area in BAT-transplanted mice by 32% compared with the sham control mice. Lipid profiles, except for serum triglyceride level, showed no difference between the 2 groups. BAT-transplanted mice showed higher concentrations of serum noradrenalin, fibroblast growth factor 21 (FGF-21), and adiponectin. Treatment with the ß3-adrenergic receptor (AR) blocker completely abrogated the atheroprotective effects of BAT transplantation, with serum concentrations of FGF-21 and adiponectin being equivalent between the 2 groups. Homologous transplantation of BAT from apoE-/- mice also showed a significant decrease in atherosclerotic lesion area by 28% without affecting lipid profiles, while epidydimal white adipose tissue transplantation did not affect atherosclerosis. Serum and endogenous BAT concentrations of FGF-21 were significantly higher in BAT-transplanted mice than sham control mice. Concomitantly, serum adiponectin levels were elevated in BAT-transplanted mice and showed a significant inverse correlation with atherosclerotic lesion area. Our findings show for the first time that atheroprotective effect of BAT transplantation is BAT-specific and independent of lipid-lowering effect, accompanied by AR-mediated activation of the FGF-21-adiponectin axis.