bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 233: Endotension: Net Flow through an Endoleak Determines its Visibility
Authors: Blackwood Stuart , Mix Doran , Wingate Mallory , Chandra Ankur , Dietzek Alan 
Published: March 2022

OBJECTIVES
Unexplained aneurysm growth despite multimodality imaging following EVAR is often attributed to endotension. We tested a hypothesis that endotension may be from a type 1a endoleak (EL) pressurizing the aneurysm sac without net forward flow, not visualized on standard angiographic imaging.

METHODS
A patient-specific aortic aneurysm phantom was constructed of polyvinyl alcohol using 3D molding techniques. A bifurcated stent graft was implanted and the phantom connected to a hemodynamic simulator for testing. Type 1a ELs were created using 7 Fr catheters. Three scenarios were studied: complete exclusion (no EL); inflow with no sac outflow; and inflow with sac outflow. DSA imaging was performed at 48kvP at 5fps followed by delayed imaging (1 frame/min) over 30 minutes.

RESULTS
With no EL, the systemic MAP (sMAP) averaged 113mmHg and Aneurysm Sac MAP (asMAP) averaged 101mmHg. (Table 1) With EL without outflow, the sMAP averaged 116mmHg and asMAP averaged 120mmHg. EL flow was bidirectional with no net forward flow. With EL with aneurysm sac outflow, the sMAP averaged 119mmHg, asMAP averaged 105.5mmHg and net EL flow was +21cc/min across the EL channel. With DSA imaging, the EL with no outflow was noted after >9 min of delayed imaging.

CONCLUSIONS
Our model demonstrated a Type Ia EL in the absence of aneurysm sac outflow resulting in full pressurization of the aneurysm sac with biphasic (zero net) flow. This EL was not visible on standard contrast DSA until >9 min. This model may serve as a first step in explaining both the mystery of endotension and in vivo aneurysm sac growth with no detectable ELs using current standard imaging modalities.
Abstract 248: Role of Mitochondrial Heat-Shock Protein 90 (HSP90) in Regulation of Vascular Smooth Muscle Cell (VSMC) Apoptosis and Vascular Remodeling in-vivo
Authors: Runge Sara , Chen Mian , Chatterjee Anuran , Miyahara Takuya , Altieri Dario , Conte Michael 
Published: March 2022

Introduction
Apoptosis of VSMC is a common feature of vascular remodeling. Mitochondrial apoptosis is regulated by an organelle-specific network including Hsp90 family proteins. Gamitrinib (G4) is a small molecule that selectively targets mitochondrial Hsp90 and has shown antitumor activity. We investigated the effects of G4 on mitochondrial membrane potential (MMP) and apoptosis in VSMC, and on vascular remodeling in vivo.

Methods
Primary cultured human VSMCs were treated with G4, 17-AAG (inhibits cytosolic Hsp90), or vehicle. MMP (TMRM assay), apoptosis (Annexin V/PI flow cytometry) and cell viability (MTT assay) were measured. For in vivo studies, a mouse carotid artery ligation model was used. Mice (N= 45) were treated with systemic G4 (10 mg/kg IP daily) vs. control, and sacrificed at 3 or 14 days.

Results
Pre-treatment of VSMC with G4 (1 uM) resulted in a rapid, dose-dependent loss of MMP upon exposure to peroxynitrite (PN;25-200 uM), compared to 17-AAG or vehicle. G4 (25 uM) sensitized VSMC to apoptotic death (17.5% vs 8.8%, p=.02) following exposure to PN (300 uM, 4 hrs). In-vivo, G4 treatment resulted in increased apoptosis (TUNEL) in the ligated carotid artery (21% vs 4 %, p=.02) at 3 days, with no discernible difference in proliferation (Ki67 and BrdU). At 14 days, G4 treatment resulted in improved remodeling, with reduced intimal thickness (25%, p=.04) and increased radius:wall thickness ratio (50%; p=.008; Figure).

Conclusions
Selective targeting of mitochondrial Hsp90 sensitizes VSMC to mitochondrial depolarization and apoptosis, and alters vascular remodeling in-vivo. This may represent a new molecular target to modulate vascular injury.
Abstract 252: Method to Quantify Femoropopliteal Artery Deformation During Knee Flexion
Authors: Kamenskiy Alexey V , Lomneth Carol S , Pipinos Iraklis I , Longo G. Matthew , Johanning Jason M , Baxter B. Timothy , MacTaggart Jason N 
Published: March 2022

Introduction
High failure rates of femoropopliteal reconstructions are commonly attributed to deformations and forces exerted on the artery during movement. The purpose of this study was to develop a method to better quantify these deformations.

Methods

Custom-made stainless steel markers were deployed in an
in situ
cadaveric femoropopliteal artery. The artery was then infused with contrast and CT images of the straight and bent (45°, 90°, 135°) leg were acquired. 3D reconstructions of the leg were created using Mimics and identification of the marker position and geometry enabled measurements of axial extension, compression, bending and torsion. After imaging, the artery was surgically exposed, photographed and excised for histological analysis.

Results
The femoropopliteal artery deformed non-uniformly along its length. No changes with knee flexion were seen proximal to the adductor hiatus and radial compression was minimal throughout the length of the artery. At the adductor hiatus the artery experienced 45° angle of twist, but no axial compression or bending. Distally, buckling and axial compression (36%) were demonstrated, but no torsion. Histology demonstrated intimal thickening corresponding to areas with the largest deformations (Figure 1).

Conclusions
This method allows quantification of non-uniform arterial deformation in the femoropopliteal artery with knee flexion. This information may assist in the design of better reconstruction techniques and devices for treatment of femoropopliteal arterial disease.
Abstract 276: Nicotine Infusion Fails to Induce Abdominal Aortic Aneurysmsin LDL Receptor Deficient Mice
Authors: Xu Yinchuan , Lu Hong , Howatt Deborah A , Balakrishnan Anju , Moorleghen Jessica J , Cassis Lisa A , Daugherty Alan 
Published: March 2022

Background and Objective
Smoking is a major risk factor for the development of abdominal aortic aneurysms (AAA). Although there are a large number of chemical constituents of smoke, recent evidence demonstrated that nicotine infusion to apoE -/- mice induces AAA formation. These nicotine-induced AAAs share many characteristics to those formed during infusion of angiotensin II (AngII). The purpose of this study was to contrast the susceptibility of AAAs induced by nicotine versus AngII in LDL receptor -/- mice.

Methods and Results
Ten-week-old male LDL receptor -/- mice were fed a saturated-fat supplemented diet for 7 weeks. One week after the initiation of the fat-enriched diet feeding, mice were randomized into 3 groups: saline infusion (N = 5), AngII (1 μg/kg/min; N = 5) infusion, and nicotine (5 μg/kg/min; N = 10) infusion, respectively, for 6 weeks. Infusions were performed using mini-osmotic pumps implanted subcutaneously. Cotinine is the major metabolite of nicotine. Plasma concentrations of cotinine were undetectable in saline and AngII-infused mice, but were at detectable levels (87 ± 28 ng/ml) in nicotine-infused mice. Despite measurable plasma concentrations of cotinine, nicotine infusion had no effect on body weight, systolic blood pressure, plasma total cholesterol concentrations, and lipoprotein-cholesterol distribution. Also, we were unable to discern any nicotine-induced changes in the lumen diameter of suprarenal aortas in live mice using high frequency ultrasound or maximum width of suprarenal aortas (0.94 ± 0.02 mm) measured ex vivo after termination. In contrast, AngII infusion promoted aortic rupture (N = 2/5 = 40%) and profoundly increased maximal width of suprarenal aortas (1.83 ± 0.20 mm) compared to mice infused with saline (0.91 ± 0.04 mm).

Conclusion
In contrast to AngII, infusion of nicotine does not induce AAA formation in LDL receptor -/- mice.
Abstract 278: Protective Effects of Niacin in a Murine Model of Abdominal Aortic Aneurysms
Authors: Thompson Allie , Robbins Nathan , Mann Adrien , Chatterjee Tapan , Batra Neil , Weintraub Neal , Blomkalns Andra 
Published: March 2022

Introduction.
Abdominal aortic aneurysms (AAAs) are common among the aging population, yet there is no effective pharmacotherapy. Neutrophils play a key role in the pathogenesis of AAA, by triggering inflammation, oxidative stress, matrix degradation and smooth muscle cell (SMC) death. Niacin, a vitamin with beneficial cardiovascular effects, was shown previously to reduce vascular neutrophil infiltration, MPO accumulation, and HOCl-induced endothelial dysfunction in a rabbit perivascular injury model.

Hypothesis
We hypothesized that niacin would have beneficial effects to prevent AAA in a mouse model.

Methods

LDL null mice were infused with angiotensin II (1000 ng/kg/min) for 14 days to induce AAA with (n=27) or without (n=18) 0.3% supplemental niacin in the drinking water. One group (n=6) received the DP1 receptor antagonist, laropiprant, in addition to niacin. We also investigated the effects of niacin on MMP release in a human neutrophil cell line (HL-60) and on viability of a murine SMC line (MOVAS-1) challenged with 100μM H
2
O
2
.

Results

Niacin decreased the rate of AAA formation as compared to untreated control mice, 26% vs. 83%, respectively. In mice that survived the complete 14 day treatment period and did not die due to a ruptured AAA, the mean suprarenal aorta diameters were 1.20 mm (SEM 0.09) in niacin treated mice vs. 1.68 mm (SEM 0.12) in the control group, representing a niacin treatment effect of a 29% diameter decrease (p<0.5). Laropiprant did not have an effect on AAA formation, however did increase the blood pressure moderately. In HL-60 cells stimulated with TNF-α, niacin (10mM) decreased MMP 9 activity by 88% but had no effect on cell viability. In MOVAS-1 cells exposed to hydrogen peroxide, 10mM niacin had a protective effect, reducing cell death at 12 hours (50% dead cells with niacin + H
2
O
2
vs. 93% dead cells with hydrogen peroxide alone, p=0.02).

Conclusions
We conclude that niacin decreases the incidence of AAA and demonstrates pleiotropic effects on neutrophils and SMCs that may underlie its already known beneficial lipid modifying mechanisms. These novel findings suggest that niacin might be a safe, effective and inexpensive medical therapy for AAA.
Abstract 295: Macrophages Induce Apoptosis of Arterial Smooth Muscle Cells via a Monocyte Chemoattractant Protein-1 (MCP-1) Mediated Cytotoxicity
Authors: Wang Qiwei , Morgan Stephanie , Ren Jun , Liu Bo 
Published: March 2022

Objectives
Excessive apoptosis of smooth muscle cells (SMCs) has been observed in human and experimental abdominal aortic aneurysm (AAA). We have previously demonstrated in a murine model of AAA that apoptotic SMCs attract monocytes and other leukocytes by producing MCP-1. In this study, we hypothesized that MCP-1 may contribute to aortic destruction also by enhancing pro-apoptotic capability of infiltrating macrophages.

Methods and Results
In a co-culture system MCP-1 primed RAW264.7 macrophages caused significantly more apoptosis of SMCs compared to control macrophages (1.53±0.11 fold increase in % of Annexin V PE+/7AAD-/CD11b- cells, n=5, p<0.05). To understand how MCP-1 may modulate cytotoxicity, we treated RAW cells with MCP-1 and analyzed Fas Ligand (FasL) expression by real-time PCR and flow cytometry. MCP-1 enhanced FasL mRNA level by 1.60±0.15 fold (p<0.05, n=4) and membrane FasL expression by 1.62±0.20 fold (p<0.05, n=3). Neutralizing FasL blocked SMC apoptosis. Consistently, we found MCP-1 elevated levels of cleaved caspase 8 and 3 in SMCs exposed to MCP-1 primed macrophages. We hypothesize that MCP-1 primed macrophages kill SMCs through a FasL-Fas-Caspase8- receptor interacting protein-1 (RIP1) mediated mechanism. Silencing RIP1 conferred apoptosis resistant to SMCs, protected them from being killed by macrophages. In situ proximity ligation assay showed that the exposed SMCs contained higher levels of RIP1-Caspase 8 complexes. In the mouse elastase injury model of aneurysm, immuno co-staining showed that TUNEL-positive SMCs were frequently surrounded by CD68+ macrophages, although little engulfing activity was observed. In parallel, aneurysm induction increased the level of RIP1-Caspase 8 complexes in medial SMCs, indirectly proved the occurrence of FasL mediated-kill of SMCs during aneurysm development.

Conclusions
Taken together, our data suggest that MCP-1 not only attract monocytes/macrophages but also can modulate their function. Mechanistically, MCP-1 primes macrophages by increasing levels of membrane bound FasL. Since apoptotic SMCs release MCP-1 in large quantity, this newly described role of MCP-1 may indicate a positive feedback loop between residential SMCs and infiltrating macrophages.
Abstract 302: Smooth Muscle Cell Mineralocorticoid Receptors Directly Mediate Aldosterone-induced Remodeling After Vascular Injury Via Type 1 Vegf Receptors
Authors: Pruthi Dafina 
Published: March 2022

Background and Significance
Endothelial damage initiates vascular remodeling with smooth muscle cell (SMC) proliferation and vascular fibrosis. Excessive remodeling, as in restenosis after vascular procedures or atherosclerosis, limits blood flow to distal tissues. In animals, aldosterone (aldo) infusion enhances remodeling which is reversed by aldo antagonists, implicating the mineralocorticoid receptor (MR). We previously showed that MR is expressed in SMC and that aldo induces the type 1 VEGF receptor (VEGFR1) in injured vessels.

Hypothesis and Results

We hypothesize that aldo promotes pathological vascular remodeling by directly activating MR in SMC and promoting SMC proliferation via VEGFR1 signaling. We show
in vivo
that aldo does not affect re-endothelialization after injury supporting our focus on SMC. To test this hypothesis we measured aldo-induced remodeling after wire carotid injury in mice with inducible SMC-specific deletion of MR (SMC-MR-KO). The 80% increase in SMC proliferation with aldo in control littermates is completely prevented in SMC-MR-KO mice (p<0.005, n=11). To examine the mechanism, mouse carotid SMC were treated with aldo
in vitro
producing a dose dependent proliferative response (1,5,10 and100nM aldo, 9%±2, 17%±3, 21%±6, and 25%±7 vs control, respectively, p<0.05, n=8). The increase in proliferation with 10 nM aldo+IgG was completely inhibited by treatment with specific VEGFR1-blocking antibody (Ab, p=0.04, n=8). Immunohistochemistry of carotid vessels reveals that VEGFR1 is induced in SMC after injury and further enhanced by aldo (55%±0.5 increase with injury, 74%± 0.5 with aldo+injury vs uninjured control, p<0.05, n=8).We examined the role of VEGFR1
in vivo
and VEGFR1 blockade significantly reduces aldo-induced SMC proliferation after injury (46%±4 decrease vs aldo+IgG, p<0.05, n=9). Tail cuff measurements reveal no difference in blood pressure with any of the treatments.

Conclusions
These data support that SMC MR directly mediates aldo-induced vascular remodeling independent blood pressure. The mechanism involves VEGFR1 that is induced on SMC in the area of injury. This study supports exploring VEGFR1-blocking drugs to prevent pathological vascular remodeling induced by aldo in humans.
Abstract 329: Myxomavirus-derived Serpin Prolongs Survival and Reduces Vasculitis in MHV68 Infected Mice by Enhancing IL-10
Authors: Chen Hao , Zheng Donghang , Liying Liu , Mee Y Bartee , Davids Jennifer , Davids Jennifer , Macaulay Colin , McFadden Grant , Thoburn Robert , Lomas David A , Virgin Herbert W , Lucas Alexandra 
Published: March 2022

Background

Lethal viral infections produce widespread inflammation with vascular leaking, clotting and bleeding (DIC), and high mortality. Serine proteases in clot-forming (thrombotic) and clot-dissolving (thrombolytic) cascades are activated by a cytokine storm and also induce systemic inflammation. Normal host
ser
ine
p
roteases
in
hibitor (
serpin
) regulation is lost. Serp-1 is a potent myxomavirus anti-inflammatory protein, which inhibits factor X (fX), tPA and uPA
in vitro
. Serp-1 reduces arterial inflammation and atherogenesis in many animal models and has been successfully tested in patients with unstable plaque and stent implants.

Methods and results

Purified Serp-1 protein treatment significantly improved survival in lethal murine
Gammaherpesvirus-68
(MHV68) infection in interferon gamma receptor (IFNγR) knock-out mice (N = 72 mice; P < 0.02) when given for 10 up to 30 days after infection. Treatment with a mammalian serpin, neuroserpin, that inhibits only tPA and uPA, was ineffective (N = 30 mice; P = NS). Serp-1 reduced viral antigen, lung hemorrhage, and aortic, lung and colon inflammation in MHV68 infected mice. Neuroserpin suppressed a wide swath of immune cell responses, while Serp-1 selectively increased CD11c+ splenocytes (macrophage and dendritic cells) and reduced CD11b+ tissue macrophage. Serp-1 significantly increased the IL-10 gene expression in aorta and plasma protein, whereas neuroserpin decreased IL-10. Serp-1 mediated survival in MHV68 infected mice was lost after treatment with IL-10 receptor antibody immediately post infection (N = 12 mice; P =0.014).

Conclusions
Serp-1, a unique myxomavirus-deried serpin, improves survival after lethal mouse herpesviral infection, reduces viral load, hemorrhage and arterial inflammation. Serp-1 provides a potential new therapeutic approach for lethal viral sepsis and DIC through altered FX and IL-10.
Abstract 334: Hypertensive Crisis Combined with Acute Myocardial Ischemic Injury after Glatiramer Acetate Subcutaneous Injection: A Case Presentation and Literature Review
Authors: Paulino Robert , Shi Qi , Samavedam Sandhya , Kakde Amit , Kiel Michael , Wu Huimin , Crevecoeur Louis , Jia Jihua 
Published: March 2022

Introduction
Hypertensive crisis (HC) affects more than a half million Americans each year, and leave many with irreversible injury. Despite extensive studies on HC and its complications, there remain many unrecognized risk factors and prognosticators. Physicians should perform comprehensive evaluation, including a current medication list review of patients who present with HC to effectively identify the cause and intervene accordingly. We present a case of HC with acute myocardial damage after subcutaneous injection of glatiramer acetate
Case presentation
A 47 year-old Caucasian male with history of multiple sclerosis (MS) who presented to the emergency room with complaints of headache, chest discomfort, and cough with frothy bloody secretions approximately 30 minutes after subcutaneous injection of glatiramer acetate. For the past 5 years, the patient had reported occasional hot flashes, headache, and palpitations after injection of glatiramer acetate. On examination, blood pressure was 260/160mmHg and heart rate was 120bpm. Chest X-ray showed acute pulmonary edema. EKG showed significant ST elevations in leads I and AVL and ST depressions in leads II, III, and AVF. Troponin levels were elevated during first 24 hours (0.1, 3.7, and 3.5 μg/L). Echocardiography revealed an ejection fraction of 45% with left ventricular wall hypokinesis. Blood pressure was controlled with intravenous nitroprusside and labetalol and after 48hours, repeat EKG was normal, and stress test with myoview was negative for ischemic changes.

Discussion
Hypertensive crisis is associated with significant morbidity and mortality. Myocardial damage often results from HC and causes subsequent heart failure which leads to death of sufferers. Glatiramer acetate (Copaxone) is an immunomodulator currently used to reduce symptomatic episodes in patients with relapsing-remitting MS. During the post-marketing period, there have been reports of patients with hypertension, chest pain, and others symptoms that received emergency medical care; however, HC combined with acute myocardial damage has been never reported. Whether an immunologic or non-immunologic mechanism mediates these episodes is unknown.
Abstract 336: Overrepresentation of Familial Hypercholesterolemia-causing Mutations in Patients with Familial Combined Hyperlipidemia
Authors: Bamimore Mary A , Cao Henian , Wang Jian , McIntyre Adam , Johansen Christopher , Hegele Robert A 
Published: March 2022

Background_
Elevated plasma low-density lipoprotein (LDL) cholesterol is a feature of both familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). FH is predominantly a monogenic _autosomal dominant_ condition that results from mutations in the genes coding for low density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). In contrast, the genetic basis of FCH, a very common dyslipidemia in the human population, is less well understood, but is considered to be polygenic. Investigations in other polygenic lipid disorders indicate that genetic susceptibility is comprised of both common polymorphisms and rare heterozygous mutations. Re-sequencing technologies have identified greater accumulation of missense rare variants in candidate genes of diseased cohorts relative to healthy controls, thus indicating a potential role of candidate genes in disease etiology.

Objective_
Our aim was to understand the genetic etiology of FCH. We hypothesized missense rare variants in the 3 known autosomal dominant FH-causing genes and the newly characterized inducible degrader of the low density lipoprotein receptor (IDOL), would accumulate in FCH patients (n=138) (cases) relative to controls (n=94). We tested this hypothesis using Sanger sequencing of coding sequences, intron-exon boundaries and some regulatory regions of the 4 candidate genes.

Results & Discussion_
For cases vs controls, the total missense rare variant carrier counts were 7/138 vs 4/94 in LDLR and 14/138 vs 9/94 in APOB. Of all these missense rare variants found in our entire cohort, we found functionally verified FH-causing variants only in our cases and not in our controls (P =0.09), namely LDLR G314S, D333V, V806I and APOB R3500W variants. These variants likely explain hypercholesterolemia in those particular FCH patients.

Conclusions_
This preliminary analysis of FCH candidate gene sequences supports the idea that rare FH-causing mutations are over-represented in FCH. The findings also support future expanded case-control and family studies to identify possible monogenic causes of FCH using various next-generation sequencing technologies.