bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 470: Aip1 Suppresses Atherosclerosis by Limiting Hyperlipidemia-Induced Inflammation and Vascular Endothelial Dysfunction
Authors: Min Wang , Huang Qunhua , Zhou Jenny Huanjiao , Qin Lingfeng 
Published: March 2022

Objective-
Apoptosis signal-regulating kinase 1 (ASK1)-interacting protein-1 (AIP1) is a signaling adaptor molecule implicated in stress and apoptotic signaling induced by proinflammatory mediators. However, its function in atherosclerosis has not been established. In the present study, we use AIP1-null (AIP1-/-) mice to examine its effect on atherosclerotic lesions in an ApoE-null (ApoE-/-) mouse model of atherosclerosis.

Methods and Results-
ApoE-/- control mice developed atherosclerosis in the aortic roots and descending aortas upon Western-type diet for 10 weeks, while the atherosclerotic lesions are significantly augmented in ApoE-/-AIP1-/- double knockout (DKO) mice. DKO mice show increases in plasma inflammatory cytokines with no significant alterations in body weight, total cholesterol levels or lipoprotein profiles. Aortas in DKO mice show increased inflammation and endothelial cell (EC) dysfunction with NF-κB activity, correlating with increased accumulation of macrophages in the lesion area. Importantly, macrophages from DKO donors are not sufficient to augment inflammatory responses and atherogenesis when transferred to ApoE-KO recipients. Mechanistic studies suggest that AIP1 is highly expressed in aortic EC but not in macrophages, and AIP1 deletion in EC significantly enhance oxidized LDL-induced NF-κB signaling, gene expression of inflammatory molecules and monocyte adhesion, suggesting that vascular EC are responsible for the increased inflammatory responses observed in DKO mice.

Conclusion-
Our data demonstrate that loss of AIP1 in aortic EC primarily contributes to the exacerbated lesion expansion in the ApoE-/-AIP1-/- mice, revealing an important role of AIP1 in limiting inflammation, EC dysfunction and atherosclerosis.
Abstract 481: Athero-metabolic and Inflammatory Alterations Promote In-stent Restenosis in ApolipoproteinE Deficient Rats
Authors: Borinski Mauricio , Simsekyilmaz Sakine , Afify Mamdouh , Flege Christian , Krott Nicole , Marx Nikolaus , Vogt Felix 
Published: March 2022

Purpose
Recently, Apoliprotein E deficient (ApoE-/-) rats have been generated by genetic manipulation, while the bench-to-bedside relevance of this novel model for coronary stenosis research has not been elucidated. Here, we seek to characterize vascular inflammation and in-stent cross-sectional stenosis (ICS) development in the abdominal aorta of ApoE-/- rats.

Methods
Trans-abdominal aorta bare-metal stent (Multi-LinkMini Vision, Abbott Vascular Inc., Santa Clara, CA; 2.5 x 8 mm; 12 atm) implantation was performed in ApoE-/- rats (Sigma Aldrich Genetic Engineering, Saint Louis, MO). At 7 and 28 days, quantification of ICS, neointimal (NI) area, injury score and inflammation score was conducted using image analysis software (DISKUS, Hilgers, Königswinter). Blood serum analysis for Interleukin (IL)-6, -8 and -10 and for cholesterol levels was performed.

Results
Serum cholesterol levels were elevated in ApoE-/- rats (8.63±1.73mmol/l vs. 1.98±0.55mmol/l; p<0.001) as compared to ApoE+/+ rats. IL-6 and (294.7±80.2pg/ml vs. 187.2±2.8pg/ml; p<0.05) and IL-8/CXCL8 (767.5±127.5pg/ml vs. 342.0±39.7pg/ml; p<0.05) were upregulated, while IL-10/cytokine-synthesis inhibitory factor was downregulated (16.8±1.4pg/ml vs. 90.7±6.5pg/ml; p<0.001) in ApoE-/- rats. After stent implantation, injury scores were similar in all groups. At 7 days, ICS (11.1±1.9% vs. 2.1±0.5%; p<0.01) and NI area (0.59±0.09mm2 vs. 0.075±0.02mm2; p<0.01) was increased as compared to controls; concomitantly, at 28 days, ICS (26.6±3.9% vs. 13.1±1.9%; p<0.001) and NI area (1.47±0.37mm2 vs. 0.54±0.10mm2; p<0.01) were elevated. Furthermore, infiltration by chronic inflammatory cells was increased in ApoE-/- rats at 28 days (456.2±181.4 vs. 108.0±25.9 per high power field; p<0.05).

Conclusions
In ApoE-/- rats, cholesterol levels as well as pro-inflammatory IL-6 and -8 are upregulated, while anti-inflammatory IL-10 is downregulated. Concomitantly, ApoE-/- rats develop increased ICS after abdominal stent implantation. This novel small animal model enables the characterization of distinctive molecular and mechanical ICS mechanisms in an atherogenic milieu that, notably, renders disposable any miniaturization of tested stents as opposed to mouse models.
Abstract 485: Percutaneous Catheter-directed Local Thrombolysis of Arterial, Venous and Shunt Thrombus Using Tissue Plasminogen Activator in Critically-ill Children - A Single Center Experience
Authors: Singh Dhiraj , Ross-Ascuitto Nancy , Siwik Ernest , Ascuitto Robert , Sernich Steffan 
Published: March 2022

OBJECTIVE
To retrospectively determine the success and complication of local catheter directed thrombolysis using recombinant tissue plasminogen activator (rTPA) in critically ill children with acute arterial, venous or shunt thrombus.

BACKGROUND
Local catheter directed thrombolysis is a well-described treatment modality for thrombotic events in adults, with maximal thrombolytic effect and minimal systemic sequelae. However, this treatment option in life threatening thrombosis is not well defined in pediatrics.

METHOD
We report an observational study in a retrospective cohort (2008-2013) of 14 cases presenting with sudden life threatening thrombosis, necessitating immediate intervention. All patients had >95% vascular/shunt occlusion which was treated with percutaneous catheter-based procedure, and rTPA administration directly at site of thrombus. The efficacy, dosage, duration, additional endovascular intervention and complications of this approach are reported.

RESULTS
The median age was 1.7 months (range, 10 days - 29 years) and median weight was 4.4 kilograms (range, 2.2 - 101 kg). Nine (64%) patients presented with shunt (Sano or aorto-pulmonary) thrombosis, three (22%) with arterial thrombosis and two (14%) with venous thromboembolism. All patients received a local bolus of rTPA [median dose 0.24 mg/kg (range, 0.01 - 1.0 mg/kg)]. Eight (57%) received an additional infusion of rTPA [median dose 0.17 mg/kg/hr (range, 0.02 - 1.0 mg/kg/hr)] of varying duration [median 1.3 hours (range, 0.3 - 18 hours)]; one patient received a prior systemic bolus of rTPA. Anticoagulation was administered in 12 (86%) and supplementary endovascular intervention (balloon angioplasty and/or stenting) was done in 4 (28%) patients. Thrombolytic success (defined as >95% return of antegrade flow) was achieved in 13 (93%). No major bleeding or other serious complication directly related to this approach occurred.

CONCLUSION
Catheter-directed local thrombolysis with rTPA can be accomplished rapidly in critical thrombosis, as a pragmatic alternative to surgery. This approach can offer satisfactory short term palliation without significant complications and improve outcome in children with life threatening thrombosis.
Abstract 487: Aspirin Treatment Hampers the Use of Plasma MicroRNA-126 as Biomarker for the Progression of Vascular Disease
Authors: de Boer Hetty C , van Solingen Coen , Prins Jurrien , Duijs Jacques M , Huisman Menno V , Rabelink Ton J , van Zonneveld Anton Jan 
Published: March 2022

Rationale
MicroRNA-126 (miR-126) facilitates angiogenesis and regulates endothelial cell function. Recent data suggest that miR-126 can serve as a biomarker for cardiovascular disease. Although endothelial cells are enriched for miR-126, platelets also comprise a major pool of miR-126. We investigated the contribution of platelets to the level of miR-126 circulating in the plasma from patients with type 2 diabetes and how this level is affected by aspirin.

Methods & Results

In vitro
platelet activation resulted in the transfer of miR-126 from the platelet- to the plasma-compartment, which was prevented by aspirin.
In vivo
platelet activation was studied in patients with type 2 diabetes, who exhibit disease-mediated platelet activation and are prone to develop cardiovascular disease. Platelet activation was monitored by measuring soluble P-selectin in plasma and correlated significantly with circulating levels of miR-126. Administration of aspirin to the patients in a randomized, placebo-controlled cross-over design, resulted in platelet inhibition and concomitantly reduced circulating levels of platelet-derived microRNAs including miR-126.

Conclusion
The profile of circulating miRs constitutes a fingerprint of activated platelets rather then activated endothelial cells. In particular miR-126 can be derived from activated platelets and the circulating levels of this miRNA can be markedly reduced when aspirin is used in patho-physiological conditions associated with platelet activation such as diabetes type 2. Therefore, the use of platelet inhibitors should be taken into account when using plasma-levels of miR-126 as a biomarker.
Abstract 492: Docosahexaenoic Acid-Enriched and Oleic Acid-Enriched Canola Oils Reduce Whole Blood Nuclear Factor Kappa-B Gene Expression in Men and Women with Abdominal Obesity
Authors: Labonté Marie-Ève , Couture Patrick , Jenkins David J , Connelly Philip , West Sheila , Kris-Etherton Penny , Jones Peter , Lamarche Benoît 
Published: March 2022

Introduction
As part of the large Canola Oil Multicenter Intervention Trial (COMIT) study, we have recently shown that consumption of a canola oil enriched with docosahexaenoic acid (DHA) under strictly controlled feeding conditions exerts anti-inflammatory effects compared with a control diet rich in linoleic acid (LA) and a diet rich in flax oil and alpha-linolenic acid (ALA).

Objective
In this study, we have investigated the impact of different oils containing various amounts of ALA, LA, oleic acid (OA) and DHA on the expression of key pro- and anti-inflammatory genes in a subset of adults having participated in COMIT.

Methods
COMIT is a randomized, crossover controlled full feeding trial involving 118 men and women with abdominal obesity and at least one other component of the metabolic syndrome who consumed 5 experimental isoenergetic diets (15.5% protein; 35.7% fat; 50.6% carbohydrate) for 4 weeks each. Here we report the impact of 4 of those 5 diets, which provided 60 g/3000 kcal of different oils: 1- High LA corn/safflower oil (CONTROL, 10.6 g OA; 0.2 g ALA; 41.6 g LA), 2- High ALA flax/safflower oil (FLAX, 10.7 g OA; 19.2 g ALA; 22.5 g LA), 3- High oleic canola (HO-CAN, 42.8 g OA; 1.4 g ALA; 8.8 g LA), 4- High DHA canola (DHA-CAN, 37.9 g OA; 1.2 g ALA; 7.6 g LA; 3.5 g DHA). Inflammatory genes expression in whole blood cells was assessed by real-time polymerase chain reaction from samples collected at the end of each diet in a random subset of 10 individuals (6 men, 4 women).

Results

DHA-CAN lowered the mRNA expression of the nuclear transcription factor kappa-B (NF-[[Unable to Display Character: &#1082;]]B) compared with CONTROL (-15.2%,
P
=0.07) and FLAX (-22.4%,
P
=0.007). NF-[[Unable to Display Character: &#1082;]]B gene expression was also lower after HO-CAN compared with FLAX (-16.5%,
P
=0.02). There was no apparent between-diet difference in mRNA expression of other inflammatory genes (interleukin (IL)-18, IL-1β, tumor necrosis factor-α) and transcription factors (natriuretic peptide receptor C).

Conclusions
Data from this controlled feeding study suggest that anti-inflammatory effects of a DHA-enriched canola oil and oleic acid-enriched canola oil compared with polyunsaturated fatty acids from plant sources are mediated, at least partly, through an alteration in the NF-[[Unable to Display Character: &#1082;]]B pathway.
Abstract 493: The Regulation of Thrombospondin-1 Release through SIRPa-CD47 Mediated-Signaling in Platelets
Authors: Clark Katherine A , Johnston Ian , Raouva Lubica , Fishbein Ilia , Levy Robert , Stachelek Stanley 
Published: March 2022

Introduction
Decreasing the inflammatory response to medical devices remains an unmet clinical need. Our group has recent evidence that CD47, a ubiquitous transmembrane protein that serves as a self-marker via interactions with its receptor, Signal Regulatory Protein alpha (SIRP-α), confers significant anti-inflammatory properties on synthetic surfaces. Also, our group was the first to find the presence of SIRP-α on platelets. Interestingly, platelets are the primary source of Thrombospondin-1 (TSP-1), a CD47 ligand involved in pro-inflammatory processes. These experiments test the hypothesis that SIRPα-CD47 mediated signaling in platelets, in part, regulates TSP-1 release.

Methods and Results
As our group previously published, clinical-grade PVC tubing was modified via a photo-activated polymer with recombinant human CD47. Citrated whole blood or platelet-rich plasma (PRP), (30 cc), was obtained from healthy volunteers and added to the unmodified and CD47-modified tubing. The blood or PRP was perfused, via a Chandler Loop apparatus, over the PVC surfaces for 3 hours. All samples were then processed for platelet poor plasma, and TSP-1 expression was analyzed via western blot and ELISA. Confirmed with western blot and densitometry, when whole blood was exposed to CD47-coated PVC, TSP-1 concentration (as compared to the percent of the time-zero control) was consistently reduced compared to that of unmodified PVC (CD47: 78.42% ± 5.62, PVC: 189.87% ± 28.95). In contrast, when PRP was exposed under analogous conditions, there was no significant difference in TSP-1 concentration (CD47: 2.55% ± 1.02, PVC: 2.72% ± 0.81). To ensure that changes in TSP-1 concentration were not the result of TSP-1 adsorption to the CD47-modified surface, proteins were eluted from the luminal tube surface, and western blot analysis confirmed a 30% decrease in relative intensity from the CD47-coated PVC compared to that of unmodified PVC.

Conclusion
CD47-modified PVC tubing significantly decreases TSP-1 levels in isolated plasma from whole blood, suggesting that CD47 decreases platelet activation. However, work so far with PRP suggests that platelet TSP-1 release is mediated indirectly through monocytes. Further work on this cascade includes SEM analysis of PVC tubing.
Abstract 504: Drug-Eluting Stent Placement for Treatment of Below-The-Knee Critical Limb Ischemia: A Report of Parameter for Wound Healing with Measurement of Transcutaneous Oxygen Tension
Authors: Junpaparp Parichart , Wongpraparut Nattawut , Chinsakchai Kamin , Ruangsetakit Chanean , Pongakasira Rungtiwa 
Published: March 2022

Objectives
The aim of this study is to evaluate the efficacy of drug-eluting stents (DES) placed below-the-knee level in the parameters for wound healing.

Background
Critical limb ischemia (CLI) has a serious impact on quality of life with a major amputation rate of 30 percent within 12 months. Endovascular treatment has been used to perform revascularization of limbs over the past decade. However, the role of drug-eluting stent (DES) placement at below-the-knee level to improve wound healing is still inconclusive.

Methods
A single center retrospective study was conducted at Faculty of Medicine, Siriraj Hospital, Mahidol University. The outcomes of infrapopliteal DES placement among forty-six patients with critical limb ischemia (category 4-6 of Rutherford’s classification) from 2007 to 2011 were retrospectively reviewed. The primary endpoints were pre- and post-procedural Ankle-Brachial index (ABI) and transcutaneous oxygen tension (TcPO2). The secondary endpoints were limb salvage rate, time-to-major amputation and healing of ulcers. The differences between pre- and post-procedural parameters were analyzed with paired T-test.

Results
The mean follow-up time in the study was 490.21 days with limb salvage rate of 93.8 percent. Complete wound healing was observed in 81.3 percent of patients. Three of the patients underwent major amputations with the time-to-amputation ranging from 40 to 277 days post-procedure. The overall ABI was significantly improved from 0.64 ± 0.12 to 0.88 ± 0.28 (p-value <0.001). Among subjects with isolated below-the-knee DES placement, ABI was also significantly improved from 0.62 ± 0.12 to 0.82 ± 0.26 (p-value 0.004). Furthermore, TcPO2 was also increased from 25.82 ± 15.77 to 40.18 ± 13.21 mmHg (p-value 0.023).

Conclusions
DES placement at below-the-knee level is both a safe and effective limb saving therapy in CLI patients. It has been shown to significantly improve parameters for wound healing: ABI and transcutaneous oxygen tension (TcPO2).
Abstract 505: Diabetic Women are Poor Responders to Exercise Rehabilitation in the Treatment of Claudication
Authors: Gardner Andrew W , Parker Donald E , Montgomery Polly S , Blevins Steve M 
Published: March 2022

Introduction.
It is not clear whether subgroups of patients with peripheral artery disease (PAD) and claudication respond more favorably to exercise rehabilitation than others. We determined whether sex and diabetes were factors associated with the response to exercise rehabilitation in patients with claudication.

Hypothesis.
Women will experience less improvement in the primary outcome measures of claudication onset time (COT) and peak walking time (PWT), that the presence of diabetes will blunt the improvement in the primary outcomes, and that the effect of diabetes will be greater in women than in men.

Methods.
Eighty patients were randomized to home-based and supervised exercise programs, and 60 completed with complete exercise intervention data. Exercise consisted of intermittent walking to near maximal claudication pain for 12 weeks. Primary outcome measures included COT and PWT. Patients were partitioned into diabetic and non-diabetic groups, and then further partitioned by sex to form four groups.

Results.
Overall, exercise adherence was high (84%), and there was no significant difference (p > 0.05) in the amount of exercise completed among the four groups. All groups had significant improvements (p < 0.05) in COT and PWT following exercise rehabilitation, except for diabetic women (p > 0.05). Only 37% of women with diabetes had an increase in COT compared to 100% of men (p < 0.01), and their risk ratio for non-response was 9.2 (p < 0.0001).

Conclusions.
Women with PAD and claudication, particularly those with diabetes, represent a vulnerable subgroup of patients who respond poorly to a program of exercise rehabilitation. Diabetic women with PAD and claudication may need greater exercise volume to achieve similar improvements in claudication measures compared to non-diabetic women and to diabetic and non-diabetic men.
Abstract 51: The Role of CCL5 in T cell Recruitment to the Aorta
Authors: Li Jie , Ley Klaus 
Published: March 2022

Introduction
T cell adaptive immunity is involved in the pathogenesis of atherosclerosis. Previously our lab found that antigen presenting cells (APCs) present antigens to effector T cells (Teff). This causes local T cell activation and cytokine production, which sustain local inflammation. However, the chemokine(s) that drive T cell recruitment into the atherosclerotic aorta are not known. By multi-color flow cytometry to analyze chemokine receptor expression on T cells from Apoe-/- aorta, we found that more than 60% of CD4+ T cells in Apoe-/- aorta express CCR5. I hypothesize that CCR5 plays an important role in T cell recruitment to atherosclerotic aortas.

Methods
T cells in the aorta of Apoe-/- mice that have been on western diet (WD) for > 3 months were analyzed by multi-color flow cytometry by staining T cell markers and chemokine receptors (CCR7, CCR5, CXCR3, CXCR6, CCR6). 400,000 Teff cells from CD45.1 Apoe-/- mice were sorted and incubated with explanted Apoe-/- aortas 12 to 18 hrs with media alone, CCL-5 (one of the ligands of CCR5) neutralizing antibody (0.5 ug/ml) or PTX (300ng/ml). Afterward, T cell infiltration into aorta was quantified by FACS. To monitor T cell-APC interaction, effector T cells from Apoe-/- mice were labeled with fluorescent dye SNARF before incubation with aortas from Apoe-/- CD11c-YFP+ mice in the above 3 conditions. Aortas were imaged by 2 photon imaging.

Results
There is a significant increase of CCR5+ T cells (63±4% of TCRβ+ T cells) in the aorta of Apoe-/- WD mice vs. Apoe-/- on chow diet (9±8%, p<0.05) or WT (13±8%, p<0.05) (n=3 in each group). CCL5 neutralizing antibody significantly decreased the number of T cells infiltrating into aorta from 997±74 (CD45.1 T cell count in the arota)(media alone) to 652±165 (P<0.05, media alone vs. α-CCL5), and PTX further decreased this number to 456±98 (p<0.05, media alone vs. PTX)(n=3 in each group). 2 photon imaging showed that T cells infiltrated into adventitia of Apoe-/- aorta and were co-localized with DCs in the aorta. Neutralizing CCL5 inhibited T cell infiltration and remaining T cells were localized mostly outside of the adventitia.

Conclusion
CCL5 plays a role in Teff recruitment into the aorta. This suggests that targeting CCR5 or its ligand CCL5 may be effective to treat atherosclerosis.
Abstract 511: Total Circulating Adiponectin Levels and its Receptors are Associated with Histological and Immunohistochemical Features of Carotid Plaque Instability
Authors: Gasbarrino Karina , Doonan Robert J. , Mantzoros Christos , Lai Chi , Veinot John , Daskalopoulou Stella S 
Published: March 2022

Introduction.
Evidence shows that low plasma levels of adiponectin, a vasculoprotective adipokine, are associated with coronary artery disease and carotid-intima media thickness. The current study investigated for the first time the association between adiponectin and carotid plaque instability, namely the association between circulating adiponectin, expression of its receptors (AR1/AR2), and plaque instability as assessed by histology/immunohistochemistry.

Methods.
100 patients scheduled for carotid endarterectomy were recruited from the Royal Victoria Hospital, Montreal. Blood samples were collected to determine total adiponectin levels. Carotid plaque specimens were stained with hematoxylin and eosin and immunostained for CD3 (lymphocytes), CD68 (macrophages/foam cells), von Willebrand Factor (vWF, neovascularization), and AR1/AR2. A vascular pathologist categorized the plaques according to AHA classification and with a semi-quantitative scale of plaque instability. The intensity and percentage of macrophages/foam cells stained with AR1/AR2 were assessed using an optical microscope scoring method.

Results.
Patients with less infiltration of CD68+ inflammatory cells in their plaques had higher levels of total circulating adiponectin (12.26 + 6.74 μg/ml) when compared to patients with greater infiltration (8.99 + 6.97 μg/ml; p=0.010). The intensity of AR1 expression on macrophages was directly associated with overall grade of inflammation and neovascularization (p=0.025 and p=0.05 respectively). A trending inverse association was noted between the percentage of macrophages expressing AR1 and overall stability (p=0.084). Expression of vWF was inversely associated with the percentage of macrophages and foam cells expressing AR2 (p=0.033 and p=0.002, respectively), while increase cap infiltration was detected in plaques with a lower intensity of AR2 expression (p=0.013).

Conclusion.
Patients whose plaques were characterized as unstable were found to have lower plasma levels of total adiponectin, a higher expression of AR1 and a lower expression of AR2 in their plaques. These results suggest a potential role for adiponectin in the development of plaque instability, as well as differential roles for its two receptors.