bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 425: Hydrogen Peroxide and 13-hydroperoxylinoleic Acid Induce the Expression of Insulin-like Growth Factor-binding Protein 3 in HepG2 Cells
Authors: Zhao Dong , Aluganti Narasimhulu Chandrakala , Selvarajan Krithika , Litvinov Dmitry , Parthasarathy Sampath 
Published: March 2022

Background
Patients with type 2 diabetes are reported to have increased oxidative stress. Oxidized LDL is reported to suppress the expression of insulin-like growth factor I receptor (IGF1R). IGF1 emerges as a potential therapeutic target for insulin resistance and deficiency. The functions of IGF1 are regulated by its receptors as well as binding proteins (IGFBPs). IGFBP3 is known as the main binding protein for IGF1, and shows inhibitory effects on IGF1 through binding to extracellular matrix. The present study investigates whether oxidative stress regulates IGF binding proteins.

Methods
HepG2 (hepatocellular carcinoma) cells were treated with either hydrogen peroxide (H2O2) or 13-hydroperoxylinoleic acid (HPODE) with/without catalase in serum free medium for 24 hours, and total RNA and protein were isolated for quantitative PCR or Western blot analyses.

Results
H2O2 of variant concentrations induced IGFBP3 expression, which was abolished by the addition of catalase. HPODE also induced IGFBP3 expression in a dose-dependent manner. The induction was found for both isoforms A and B of IGFBP3.

Conclusion
Our findings shed light on the potential synergetic regulation of IGF1 by oxidative stress through both the receptor and binding protein, and advance the understanding of the IGF1 resistance in type 2 diabetes. Furthermore, antioxidants are indicated to be able to increase the IGF1 sensitivity, and reduce the dosage and side effects of IGF1 administration for patients with diabetes.
Abstract 444: The Liver-Specific Role of Sortilin in VLDL Secretion
Authors: Patel Kevin M , Strong Alanna , Rader Daniel J 
Published: March 2022

Introduction
Sortilin, the protein product of the SORT1 gene, is a multi-ligand sorting receptor involved in Golgi to lysosome trafficking that is expressed in multiple tissues. Genome-wide association studies have shown an association between elevated SORT1 expression in human liver and a reduction in low-density lipoprotein cholesterol (LDL-C) and in myocardial infarction (MI) risk. Our lab has previously shown liver specific sortilin overexpression in mice reduces LDL by facilitating LDL plasma clearance and by promoting the lysosomal degradation of very-low density lipoprotein (VLDL). Interestingly, we and others have also shown that total body Sort1 deficiency in mice is associated with a paradoxical reduction in VLDL secretion (48%, P = 0.004). One major difference is that the overexpression studies were hepatic specific whereas the loss-of-function studies were in total body knockout (KO) mice.

Methods/Results
We used liver-specific Sort1 conditional KO mice and reconstitution of hepatic Sort1 in total body KO mice to further probe the specific role of hepatic sortilin in VLDL secretion. Sort1 fl/fl mice were injected with a control adeno-associated virus (AAV) or an AAV expressing Cre recombinase driven by a liver specific promoter and in vivo VLDL secretion studies were performed. Liver-specific Sort1 deletion reduced VLDL secretion by 51% (P = 0.005). We also used AAV to test the hypothesis that sortilin serves as a chaperone to facilitate VLDL secretion. Sort1 reconstitution in total body Sort1 KO mice reduced VLDL secretion by 29% (P = 0.002). Interestingly, expression of a sortilin mutant that cannot traffic to the lysosome but does traffic to the plasma membrane increased VLDL secretion by 88% (P = 0.001).

Conclusion
These findings suggest that liver-specificity is not responsible for the paradoxical reduction in secretion seen in the total body Sort1 KO mouse, which is reproduced in the hepatic-specific sortilin KO mouse. The differential effects of wild-type and lysosomal defective sortilin on VLDL secretion and are consistent with a model in which sortilin serves a dual function in VLDL trafficking, with low levels of sortilin facilitating VLDL export and higher levels of sortilin promoting pre-secretory lysosomal VLDL degradation.
Abstract 496: Large Pulmonary Embolism Treated with a Novel Percuatneous Catheter-Directed, Ultrasound-Assisted Low Dose Thrombolysis
Authors: Bhatheja Rohit , Ranasinghe Indika 
Published: March 2022

Background
Massive Pulmonary embolism (PE) is a life threatening diagnosis. Survival is dependent on the timing and availability of intravenous alteplase. In those who survive; recurrent PE, pulmonary hypertension and cor pulmonale are the long term sequelae.

Case
We describe a 63 year old morbidly obese male (weight 470 lbs) presenting with increasing dyspnea. A CT scan of the chest revealed massive clots in bilateral pulmonary arteries and right ventricular (RV) strain.
Approximately 6 months prior to presentation he was diagnosed to have PE and was treated with warfarin. Warfarin was discontinued after 6 months as he was asymptomatic and CT scan showed resolution of clots. In the past few weeks he started to smoke and also complained of black stools.
Due to high risk presentation, history of melena in the recent past and dyspnea at rest, he was offered percutaneous therapy for PE. Using single internal jugular venous approach, right heart catherterization and pulmonary angiography was performed. Bilaterally ultrasound assisted- thrombolysis infusion catheters were placed in the pulmonary arteries. Alteplase was infused at low dose; total dose infused was 24 mg over 19 hours (Typical intravenous dose is 100 mg). Baseline hemodynamics showed severe pulmonary hypertension. Follow up angiogram showed almost complete resolution of clots and complete improvement in symptoms. Work up revealed Anti-Thrombin III deficiency. He was treated bivalirudin and discharged on warfarin. Follow-up testing showed improved RV pressures.

Discussion

The mortality rate for acute PE is 2-6% in those with hemodynamic stability, and 30% or more in those with shock or unstable hemodynamics. Catheter-directed local thrombolysis should be considered as a therapy in those with sub-massive and massive PE with the advantage of significantly lower thrombolytic dose (almost 75% lower) with minimal bleeding risk. The ultrasound energy in this thrombolytic EKOS
@
catheter helps loosen the clot via mechaincal energy, allowing lower dose of thrombolytics to be used locally. Ongoing studies utilizing this technology such as SEATTLE-II and ULTIMA will

offer further evidence based guidelines to manage acute pulmonary embolism.
Abstract 59: Platelets Have a Central Role in T Helper Cell Development and Responses
Authors: Morrell Craig , Shi Guanfang , Field David 
Published: March 2022

Platelets are the primary cellular mediator of thrombosis, but platelets also have important roles in immune responses. Immune roles for platelets have been primarily explored in the context of endothelial cell interactions and innate immune responses, but our work now demonstrates an important and novel role for platelets in T cell development. Using the mouse abdominal cardiac transplantation model we have discovered that platelets have a central role in CD4+ T helper cell development and differentiation. Platelet deficient thrombopoietin receptor (TPOR/c-MPL) knockout mice given cardiac transplants have an accelerated rejection response driven by Th17 type of CD4+ T cell activation and infiltration of transplant tissue. These mice also have a basal skewing to Th17 development in the absence of transplantation. Platelets are the primary source of platelet factor 4 (PF4/CXCL4) and PF4-/- mice exhibit a very similar phenotype of unrestrained Th17 T cell development and responses post transplantation as the TPOR-/- mice. Furthermore, PF4 directly limits in vitro Th17 cell differentiation, demonstrating that platelets via PF4 have a major prior unrecognized role in T helper cell differentiation.
Taken together, these data demonstrate a highly novel platelet function in T helper cell development. PF4 has a direct effect on maintaining T cell homeostasis and differentiation which is highly relevant to transplant immune responses and chronic rejection.
Abstract 64: Interleukin-10 Decreases HDL: A Novel Cause of Disappearing HDL Syndrome
Authors: Freeman Lita A , Moraitis Andreas G , Shamburek Robert , Wilson Wyndham , Grant Cliona M , Rao Koneti , Price Susan , Hornung Ronald L , Fleisher Thomas , Pucino Frank , Illei Gabor G , Remaley Alan T 
Published: March 2022

Introduction
“Disappearing HDL Syndrome” refers to cases of acquired severe HDL deficiency in non-critically ill patients. Except for rare idiosyncratic drug reactions, the physiological basis of Disappearing HDL Syndrome is not understood.

Hypothesis
“Disappearing HDL” in patients with B-cell disorders may be due to increased levels of cytokines, particularly IL-10, in plasma.

Methods
We investigated cytokine levels in a patient with intravascular large B-cell lymphoma (IVLBCL) who presented with undetectable or very low HDL-C, low LDL-C and markedly elevated triglycerides. IL-10 levels were investigated in additional patients with B-cell disorders (IVLBCL, large B-cell lymphoma, and ALPS) who presented with similar lipid profiles. A direct causal role for IL-10 in modulating HDL-C was investigated with a randomized, placebo-controlled study of recombinant IL-10 infusion into psoriatic arthritis patients.

Results

All cases (IVLBCL, large B-cell lymphoma and ALPS) had highly elevated serum IL-10 levels that normalized after chemotherapy concomitant with normalization of HDL-C, LDL-C and TG. In a survey of 93 ALPS patients, IL-10 showed a strong inverse correlation with HDL-C (R
2
= 0.3720, p<0.0001). In a randomized, placebo-controlled study of recombinant IL-10 infusion into psoriatic arthritis patients HDL-C precipitously decreased to near-undetectable levels shortly after IL-10 injection. Furthermore, IL-10 treatment also decreased LDL-C by 51% or more during IL-10 administration (p < 0.005) and increased TG by up to 2-fold.

Conclusions
Our study has identified increased IL10 as a potential cause of Disappearing HDL Syndrome and demonstrated that in addition to HDL-C, IL-10 can also modulated levels of LDL-C and TG, thus identifying a new link between inflammation and lipid metabolism.
Abstract 17: Cyclooxygenase-2 Deletion Favors Deep Vein Thrombosis in Mice
Authors: Barbieri Silvia S , Tarantino Eva , Amadio Patrizia , Gianellini Sara , Mussoni Luciana , Tremoli Elena 
Published: March 2022

Deep vein thrombosis (DVT) is a common condition that often leads to pulmonary thromboembolism and death. Cyclooxygenase (COX)-1 and -2 catalyze the formation of prostaglandins and thromboxane (TX)A2 from arachidonic acid and play a critical role in the thrombotic events, however, the impact of COX-2 deletion (COX-2KO) in the DVT remains unclear. In this study, traditional (thromboelastomethry, mass weight and histology) and innovative (venous ultrasonography) approaches were used to assess the effect of COX-2 ablation on DVT in mice. In particular, ligation of the inferior vena cava to induce thrombus formation in COX-2KO and WT mice was carried out.
Thromboelastometry analyses performed in whole blood of COX-2KO revealed alterations of clotting factors, and of platelet activity, with consequent greater clot firmness and clot elasticity. COX-2KO mice have increased plasma levels of functional fibrinogen, factor VIII and tissue factor (TF), and higher TXA2 serum than WTs. Finally, PAI-1 activity was the highest in COX-2KO, whereas tPA activity was similar in the two groups. The propensity to thrombosis of COX-2KO mice was also confirmed by ultrasonography. Genetic deletion of COX-2 was associated with bigger thrombi already at early time point. At 48 hours COX-2KO thrombi showed a greater content of connective tissue and fibrin, and increased number of infiltrated monocytes compared to WT. Remarkably, Annexin A2 (ANXA2), a fibrinolytic receptor, was significantly increased in cells present in COX-2KO thrombi. In addition, peritoneal macrophages from COX-2KO mice showed increased expression of ANXA2 with different distribution at cellular level compared to WTs. In particular, ANXA2 was expressed in the cytoplasm and in the nucleus of COX-2KO macrophages, whereas in control cells the protein was found mainly localized on cell membrane/periphery.
In conclusion, the increased basal activation of haemostatic system observed in COX-2KO mice may partly explain the predisposition of these mice to thrombosis. In addition, the different localization of ANXA2 in monocytes from COX-2KO mice with respect to wild type mice suggests that this protein may display additional protective, as yet unknown, mechanisms influencing the stability of venous thrombi.
Abstract 177: A Novel Vascular "Ring" Assay for Smooth Muscle Contractility Using Magnetic 3-Dimensional Bioprinting
Authors: Tseng Hubert , Gage Jacob A , Haisler William L , Neeley Shane K , Killian T C , Barthlow Herbert G , Wagoner Matthew , Souza Glauco R 
Published: March 2022

The current standard for studying pharmacodynamics on vascular smooth muscle contractility is wire myography with ex vivo tissue, which suffers from high cost low throughput, limiting its widespread use. Yet, in vitro alternatives are insufficient, as they are commonly two-dimensional (2D) monolayers on rigid surfaces unlike the soft vasculature. Thus, a rapid, robust in vitro assay is needed that mimics the native three-dimensional (3D) environment, while yielding high data throughput.
Towards that goal, we introduce an 3D in vitro assay in which cellularized vascular "rings" are rapidly and magnetically bioprinted. In the assay, cells are incubated with magnetic nanoparticles to render them magnetic, then printed into 3D rings (1.5 x 10^5 cells/ring) in 96-well plates. The rings will then contract or dilate over a short amount of time (<5 h) in a dose-dependent manner visually similar to vessel contraction and dilation (Fig. 1A). This measurement is label-free, meaning that the rings can be experimented on afterwards to explore pharmacodynamics. Moreover, this assay is captured using an iPod-based imaging system programmed to take images of whole plates (Fig. 1B) instead of imaging individual wells under a microscope.
This assay was validated for the evaluation of drug efficacy by measuring contractility in 3D bioprinted rings of A10 rat vascular smooth muscle cells. The compounds tested were either vasodilators (blebbistatin, forskolin, verapamil) or vasoconstrictors (norepinephrine, phenylephrine, U46619). Ring contraction was compared to the presence of phosphorylated myosin light chain-2 which is related to smooth muscle concentration. Furthermore, the gene expression profiles of rings exposed to specific compounds are compared to negative controls. The result of this study is the validation of the vascular assay that rapidly prints 3D environments similar to the native blood vessel, and efficiently measures smooth muscle contraction.
Abstract 375: Mast Cell-Specific Regulation of Cardiomyocyte Contractility: Reevaluation of Role in Cardiac Function Following Myocardial Infarction
Authors: Ngkelo Anta , Richart Adele , Vilar Jose , Marck Pauline , Heymes Christophe , Rodewald Hans-Reimer , Silvestre Jean-Sebastien 
Published: March 2022

Inflammatory cells orchestrate post-ischemic cardiac remodeling after myocardial infarction (MI). Studies in Kit mutant mice suggest key roles for mast cells in post-ischemic tissue remodeling. However, Kit mutations affect multiple cell types of both immune and non-immune origin. The aim of this study was to address the impact of mast cells on cardiac function following MI, using selectively mast cell-deficient mice (Cpa3Cre/+ mice).
The number of mast cell progenitor (Lin-CD45+CD34+FcγRII/III+β7+) increased in the bone marrow and the white adipose tissue on day 3 after MI, infiltrated the heart on day 5 and differentiated to mature mast cells (Cd117+FcεRI+Sca1+) by day 7 in cardiac tissue. To assess the functional effect of mast cell infiltration, the cardiac function 14 days following MI was assessed in wild-type (WT) and 3 mast cells deficient mice models, the kitW/Wv mice, the Cpa3Cre/+ mice and mice treated with the degranulation inhibitor DSCG (50μg/g, once a day). There was a significant decrease of the left ventricular shortening fraction in all 3 mast cell deficient models compared to WT mice (1.4-, 1.6- and 2-fold respectively) that correlated with increased cardiomyocyte apoptosis in the kitW/Wv mice; and increased fibrosis in the DSCG-treated mice (n=8-14 per group, p<0.01 vs WT). Interestingly, in the Cpa3Cre/+ mice there were no differences on post-MI cardiac remodeling, but instead we observed a significant reduction in cardiomyocyte contractility (both cell shortening and maximal contracting velocity) (p<0.01) with no effect on Ca2+ transient peak or sarcoplasmic reticulum load.
This work re-evaluates existing mast-cell deficient models on their effect on cardiac remodeling and identifies a novel function for mast cells on modulation of cardiomyocyte contractility, Ca2+ cycling independently. Identification of the molecular regulators involved in the cardiac effect of mast cell will provide a new platform of regulators with potential therapeutic properties.
Abstract 519: Consumption of Energy Beverage is Associated With an Attenuation of Arterial Endothelial Flow--Mediated Dilatation
Authors: Higgins John , Yang Benjamin , Ortiz Brandon , Herrin Nikki , Doolittle Johnathan , Kahlden Kyle , Dayah Tariq , Cassel David , Ali Asif 
Published: March 2022

Introduction:
Energy drinks are being consumed more and more worldwide, and have been associated with some deaths in adolescents and young adults, especially when consumed while exercising. The consumption of energy drinks before or during exercise might be linked to an increased risk for myocardial ischemia as a symptom of endothelial dysfunction. Energy beverage consumption and its acute effect on endothelial function is not well-studied.

HYPOTHESIS
Consumption of an energy drink will acutely impair endothelial function in a young healthy adult.

Methods:
After fasting from caffeine for at least 24 h and food for at least 8 h prior, eleven healthy non-smoker medical students (9 males), average age 24.5 years (range 23-27 years), average BMI 22.8, received an ECG, blood pressure & pulse check, and underwent baseline testing (BL) of endothelial function using the technique of endothelium-dependent flow-mediated dilatation (FMD) with high-resolution ultrasound (according to recommended guidelines of the University of Wisconsin Atherosclerosis Imaging Research Program Core Laboratory). The subjects then drank an energy beverage (EB), a 24-oz can of Monster Energy Drink®, and the above was repeated at 90 min after consumption. The FMD was calculated as the ratio between the post-cuff release diameter and the baseline diameter. Each FMD image was checked for quality control, and each artery diameter was measured as the distance between opposing tunica medias by two experts. Three measurements were taken at the QRS complex, repeated on three separate beats, and then all were averaged.

Results:
The hemodynamics were as follows, BL vs EB group respectively (mean+/-SD): Heart rate 65.2+/-11.3 vs 68.2+/-11.8 beats per minute, Systolic Blood pressure 114.0+/-10.4 vs. 114.1+/-10.4 mmHg, Diastolic blood pressure 68.8+/-9.3 vs. 70.6+/-7.1 mmHg; all were not significantly different. However, consumption of the EB resulted in a significantly attenuated peak FMD response (mean+/-SD): BL group 5.9+/-4.6% vs. EB group 1.9+/-2.1%; P=0.03).

Conclusions:
Acute exposure to an energy beverage impairs arterial endothelial function in healthy young adults. Given the increased use of these beverages associated with exercise in young adults, more research is needed.
Abstract 521: Endothelial Cell Forward Migration in a Disturbed Wall Shear Stress Environment is Promoted by Rho-Kinase Inhibition
Authors: Hsiao Sarah , Tovar-Lopez Francisco , Gunn Julian , Spencer Timothy , Halliday Ian , Perrault Cecile , Evans Paul 
Published: March 2022

Stent deployment to treat coronary artery disease causes damage and loss of endothelial cells (EC). Repair of injured arteries by EC migration is co-ordinated by Rho family GTPases. It is also regulated by wall shear stress (WSS), a mechanical force exerted by flowing blood on the vessel wall, via mechanisms that are poorly understood. It was hypothesised that stent struts may impede repair of injured endothelium by inducing localised disturbances in WSS.
To simulate a stented artery in vitro, chamber slides were fabricated with ridges (100 μm high) positioned perpendicularly to the flow direction. Confluent EC monolayers seeded on one side of either ridged or non-ridged (control) chambers were exposed to flowing culture medium (Ibidi® system). Flow patterns were determined by computational fluid dynamic (CFD) modelling and particle velocimetry. Live cell imaging and analysis using ImageJ® software enabled quantification of EC migration velocity and directional persistence (DP).
EC on the non-ridged chamber slide were exposed to a uniform WSS of 13 dyn/cm2 and migrated relatively uniformly in parallel with the flow direction (average velocity 1.13 μm/min; DP 0.59). By contrast, CFD and particle velocimetry revealed spatial WSS differences over the ridged chamber, with significant spikes above physiological levels (>70 dyn/cm2) at the corners of the ridges and distinctive flow recirculation zone immediately downstream from ridges (-4 dyn/cm2). While EC were able to migrate over the ridges, cells that reached the recirculation zone displayed non-uniform directionality (DP 0.25) and reduced velocity (0.78 μm/min). Inhibition of the RhoA signalling pathway with ROCK inhibitors promoted EC forward migration within the recirculation zone by elevating DP (0.41) and velocity (1.16 μm/min).
It was concluded that disturbed WSS downstream from stent strut-like ridges prevented the forward migration of EC. Inhibition of the RhoA/ROCK signaling pathway promoted EC migration and re-population of these sites. Our data suggest that treatment using a ROCK inhibitor may promote re-endothelialisation of stented arteries.