bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 332: Genomically Enhanced Risk Stratification in Abdominal Aortic Aneurysm Repair
Authors: Ryer Evan J , Smelser Diane T , Garvin Robert P , Yoon H. R , Bernard-Eckroth Kamell R , Franklin David P , Tromp Gerard , Elmore James R , Carey David J , Kuivaniemi S. H 
Published: March 2022

OBJECTIVE
The purpose of this study was to investigate the association between selected single-nucleotide polymorphisms (SNPs), associated with abdominal aortic aneurysms (AAA) in previous genome-wide association studies, and major adverse events following AAA repair

METHODS
Genomic DNA was isolated from blood samples collected from AAA patients and used for genotyping. A genetic risk score was constructed using five SNPs known to be associated with AAA. Epidemiologic data were extracted from the electronic medical record and analyzed retrospectively. Major adverse events were defined as myocardial infarction, cardiac arrest, respiratory failure requiring tracheostomy, renal failure requiring dialysis, colonic ischemia requiring resection, limb ischemia requiring operation, multi-system organ failure or death.

RESULTS
Three hundred and twenty one patients (267 male, 83%) with complete genomic and clinical data underwent AAA repair from 2004-2012. Demographics were consistent with a standard AAA population. 204 patients (64%) underwent endovascular repair and 117 (36%) underwent conventional open surgical repair. Quality control checks were performed on the clinical and laboratory data and none of the 5 selected SNPs deviated from the Hardy-Weinberg Equilibrium. Stepwise logistic regression was then used to determine the most parsimonious model of variables associated with adverse outcomes from AAA repair. Serum creatinine, height, resting heart rate, diastolic blood pressure and the genetic risk score remained in the model. The Hosmer and Lemeshow test of deviation from goodness-of-fit (p = 0.56) indicated that the data fit the model well. The regression coefficients from this model will be used to construct a clinician-friendly risk calculator to help identify patients at increased risk for a major adverse event following AAA repair.

CONCLUSIONS
Selected SNPs help identify patients at risk for major adverse events following AAA repair. Incorporating genetic data, especially in patients with few clinical risk factors, may result in a better preoperative risk assessment.
Abstract 339: Association of the American Heart Association’s Life’s Simple 7 Metric for Cardiovascular Health with Risk of Venous Thrombosis: the Reasons for Geographic and Racial Differences in Stroke Cohort
Authors: Cushman Mary , Judd Suzanne E , McClure Leslie A , Lakoski Susan G , Folsom Aaron R , Zakai Neil A 
Published: March 2022

Background
The AHA released a metric, Life’s Simple 7 (LS7), in 2010 to track cardiovascular health. The AHA 2020 Goals include improving population levels of LS7 by 20%. LS7 classifies 7 health components into poor, intermediate or ideal levels. The 7 components are physical activity, diet, smoking, body-mass index, glucose, blood pressure and cholesterol. Associations of these individual components with risk of venous thrombosis (VT) vary in the literature, but we hypothesized a decreased risk of VT with favorable LS7 summary scores.

Methods
We recruited 30,239 black and white participants age ≥45 across the US in 2003-7. With 4.6 years of follow up we validated 278 cases of first-time VT, including deep vein thrombosis and pulmonary embolus. We considered a 14 point summary score for LS7 and divided it into inadequate (0-4 points), average (5-9 points) and optimum (10-14) cardiovascular health. Cox proportional hazards models were used to relate baseline LS7 score to risk of subsequent VT, adjusting for age, sex, race, income, education and region of residence.

Results
Cases of VT were older and more likely to be male than noncases. Across categories of optimum, average and inadequate baseline health based on the summary LS7 score, the incidence rates of VT were 1.8, 2.1 and 3.1 per 1000 person years, respectively. Compared to those with inadequate health, persons with average health had an adjusted HR of VT of 0.60 (95% CI 0.42-0.84) while those with optimum health had a HR 0.52 (95% CI 0.36-0.77). The HR for a 1 point improvement in overall score (analogous to improvement of one of the 7 factors from poor–>intermediate or intermediate–>ideal) was 0.87 (95% CI 0.81-0.94). The individual factors of LS7 most strongly related to VT risk were ideal physical activity level (HR 0.61, 95% CI 0.46-0.83) and ideal body-mass index (HR 0.42, 95% CI 0.30-0.60); these associations were independent of each other. All associations were similar in blacks and whites.

Conclusions
A summary measure of cardiovascular health was strongly associated with reduced risk of VT in this US population sample. Results suggest that lifestyle interventions might be effective in reducing incidence of VT, and that achieving AHA’s 2020 Goals will also reduce VT incidence.
Abstract 345: The Thrombotic Reactivity of Endothelial Cells from Deep Vein and Pulmonary Artery Venous Beds in Response to Thrombin
Authors: Caliste Xzabia A , Roztocil Elisa , Clarke Amanda L , Cullen John P , Gillespie David L 
Published: March 2022

Background
Pulmonary embolism (PE) is thought to occur largely due to deep venous thrombosis from the lower extremities. A portion of PEs however may result from primary pulmonary artery thrombosis. Recent studies have shown pulmonary artery endothelial cells have increased fibrinolytic reactivity compared to iliac vein endothelial cells in response to TNFα stimulation, a cytokine known to be up-regulated in the systemic response to trauma. The goal of this study was to determine if similar thrombotic stimuli occurs in non-trauma situations.

Methods
Human iliac vein endothelial cells (HIVEC) and human pulmonary artery endothelial cells (HPAEC) were incubated at 37° C in the presence or absence of 25pM thrombin for 24 hours. Plasminogen activator inhibitor-1 (PAI-1), uPA, tPA, EPCR, PAR-1 and TM expression in cell lysates were evaluated by Western blot analysis. ICAM-1 cell surface expression was evaluated by flow cytometry.

Results
While thrombin had no effect on the expression of uPA in HPAEC, there was a ~15% decrease in expression in HIVEC. With tPA, HPAEC and HIVEC had an 11% and ~25% increase in expression, respectively. In contrast, thrombin stimulation caused a decrease in PAI-1 expression in HPAEC while having no effect on HIVEC. There was no change in EPCR expression in HPAEC, however there was a 22% decrease in HIVEC. HPAEC demonstrated decreased expression of PAR1, in contrast to an almost 40% increase in PAR1 expression in HIVEC. Thrombin produced no change in HIVEC recombinant TM expression, however, 11% increase in expression was observed in HPAEC. With ICAM-1, neither HIVEC nor HPAEC had a change in expression after thrombin stimulation.

Conclusion
This data shows that endothelium of the deep veins reacts differently from pulmonary arterial endothelium in response to non-trauma stimuli. Endothelial cells from the iliac vein and pulmonary artery venous beds differentially express markers of the fibrinolytic and coagulation pathways, and this variance in expression may play a role in the thrombotic reactivity of these vascular beds.
Abstract 352: Adeno-Associated Virus-mediated Restoration of Angiotensinogen Function in Mice With Hepatocyte-specific Deficiency
Authors: Wu Congqing , Lu Hong , Moorleghen Jessica J , Howatt Deborah A , Balakrishnan Anju , Cassis Lisa A , Daugherty Alan 
Published: March 2022

Background and Objective
We have reported previously that genetic or pharmacological inhibition of angiotensinogen (AGT) leads to resistance to dietary fat-induced body weight gain. This phenotype has not been observed in mice subject to pharmacological inhibitors of other components of the renin angiotensin system including renin, ACE, and AT1 receptors. To investigate whether restoration of AGT reverses this lean phenotype, we injected an adeno-associated virus (AAV) 2/8 vector carrying wild type AGT to mice with hepatocyte-specific deficiency of AGT (hepAGT -/-).

Methods and Results
HepAGT -/- mice were generated by disrupting AGT gene in hepatocytes via albumin promoter driven Cre recombinase expressed in mice with floxed AGT alleles. An AAV AGT vector was constructed with the insertion of wild type AGT. AAV null vector was used as control. AAV expression was driven by hepatocyte-specific thyroxine-binding globulin promoter. Five groups of male LDL receptor -/- mice at age of 8 - 10 weeks were studied: wild type (hepAGT +/+) mice received either no AAV (PBS) or null AAV, and hepAGT -/- mice received low dose (1 x 1010 genome copy), high dose (3 x 1010 genome copy), or null AAV. Four weeks after AAV injection (i.p.), all mice were fed a saturated fat-enriched diet (42% calories from milk fat) for 12 weeks. Plasma samples were collected through retro-orbital bleeding at weeks 2, 4, 8, and 16 after AAV injection. Plasma AGT concentrations peaked between weeks 2 and 4, then declined modestly, irrespective of dosage. However, at the high dose, plasma AGT concentrations in hepAGT -/- mice were comparable to those in hepAGT +/+ mice. Plasma total cholesterol concentrations, body weight gains, and systolic blood pressures were not different between hepAGT +/+ and hepAGT -/- mice receiving either dose of AGT AAV. Atherosclerosis, quantified as percent lesion area covering the intima of the aortic arch, was equivalent between hepAGT -/- mice receiving either dose of AGT AAV and hepAGT +/+ mice, whereas it was nearly absent in hepAGT -/- mice receiving null AAV.

Conclusions
AGT in an AAV 2/8 vector efficiently recovers plasma AGT concentration in hepAGT -/- mice in a dose-dependent manner. This approach permits the elucidation of structural mutations on AGT function.
Abstract 36: Array-based Profiling Reveals Biomarker and Therapeutic Potential for Different microRNAs in Patients with Symptomatic Carotid Stenosis
Authors: Osterholm Cecilia , Eken Suzanne M , Chernogubova Ekaterina , Perisic Ljubica , Razuvaev Anton , Jin Hong , Roy Joy , Hedin Ulf , Maegdefessel Lars 
Published: March 2022

The discovery of an entirely new method of recognition and regulation of gene expression and protein translation by microRNAs (miRs) has provided new hope for innovative disease discovery and therapy. Research in recent years has assigned miRs a key regulatory role during various pathological processes. Lately, their potential as biomarkers in disease received a lot of attention. Aim of the present study was to explore the role of miRs as potential regulators and plasma biomarkers in patients with carotid stenosis and at risk of stroke.
Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we were able to profile the regulation of miRs in patients with asymptomatic vs. symptomatic carotid stenosis undergoing carotid endarterectomy. A PCR-based microRNA array of plasma, sampled at the carotid lesion site, identified eight miRs (miRs-15b, -29c, -30c/d, -150, -191, -210 and -500) being substantially altered in symptomatic vs. asymptomatic patients. In peripheral plasma samples, the expression of miRs-150 and -191 remained significantly different. Using an in vitro cell streamer system, we subjected human carotid smooth muscle cells, as well as human carotid endothelial cells, to physiologic and pathologic flow conditions. Interestingly and in accordance with our findings from the initial plasma profiling study, laminar (physiologic) flow induced miR-210 up-regulation, whereas turbulent (pathologic) flow suppressed miR-210 expression in both cell lines. In addition, similar significant changes in miR-210 regulation were detectable in a model of vascular remodelling, balloon injury of the carotid artery in Sprague Dawley rats. Of importance, miR-210 targets several key genes and signalling pathways involved in vascular remodelling and atherosclerotic plaque stability.
The present study explores the diagnostic, prognostic and therapeutic potential of miR regulation in patients with symptomatic carotid stenosis and increased risk of stroke. We were able to identify miRs-150 and -191 as potential diagnostic plasma markers, and miR-210 as a key modulator of pathologic processes in atherosclerosis-related vascular remodelling.
Abstract 374: Soy Supplementation Prevents Progression of Smaller but Not Larger Atherosclerotic Plaques: Results of a Postmenopausal Monkey Reverse Translational Trial
Authors: Meléndez Giselle C , Pajewski Nicholas M , Appt Susan E , Kaplan Jay R , Register Thomas C , Clarkson Thomas B 
Published: March 2022

Rationale_
A recent clinical trial reported that soy supplementation reduced atherosclerosis progression in the carotid arteries of women who were <5 years postmenopausal, an effect not shared by women >5 years postmenopausal. Here we tested the hypothesis that soy atheroprotection may be influenced by the size of pre-existing atherosclerotic lesions at the initiation of treatment.

Methods_
Premenopausal female cynomolgus macaques (n=38) were fed an atherogenic diet (Casein/Lactalbumin [CL]) for 34 months. Animals were then ovariectomized (OVX) and the left iliac artery (LCI, a surrogate for the coronary arteries) was biopsied to determine the amount of atherosclerosis present at baseline. Immediately after OVX, monkeys were randomized to either continue consuming the CL diet (n = 20) or to consume a soy protein diet (SP, n = 18) for an additional 34 months. At necropsy, the right iliac (RCI) and coronary arteries were collected and atherosclerosis extent was quantified.

Results_

The CL diet group increased plaque size in the RCI compared to pretreatment (0.43 ± 0.06 mm
2
vs. 0.85 ± 0.12 mm
2
,
p
=0.019) whereas, plaques did not increase in size in the SP diet group, (LCI: 0.60 ± 0.10 mm
2
vs. RCI: 0.82 ± 0.16 mm
2
, p=0.17). Notably, SP diet did not have a beneficial effect on coronary artery plaque extent (CL: 0.73 ± 0.20 mm
2
vs. SP: 0.63 ± 0.16 mm
2
,
p
=NS). However, we observed that when animals were divided at the median based on pretreatment LCI plaque sizes (below; 0.21 ± 0.14 mm
2
: above; 0.82 ± 0.06 mm
2
), the SP diet prevented plaque progression in both the iliac (CL: 0.54 ± 0.14 mm
2
vs. SP: 0.19 ± 0.04 mm
2
,
p
=0.04) and coronary arteries (CL: 0.52 ± 0.11 vs. SP: 0.17 ± 0.06 mm
2
,
p
=0.04) only in animals with smaller pretreatment plaques. There was no atheroinhibition among soy treated monkeys with plaques that were above the median (RCI CL: 1.32 ± 0.11 mm
2
vs. SP: 1.35 ± 0.14,
p
=0.94 and coronary artery CL: 1.06 ± 0.11 vs. Soy: 1.00 ± 0.17,
p
=0.63).

Conclusions_
Pretreatment atherosclerosis stage is a major determinant of the potential atheroprotective effect of soy treatment. These data suggest that to obtain cardiovascular benefits of soy supplements, treatment should begin during the perimenopausal transition or in the very early postmenopause while plaques are usually still small.
Abstract 376: Platelet Depletion Accelerates the Vulnerability of Early Atherosclerosis in Apolipoprotein E-Deficient Mice
Authors: Li Rong , Ren Meiping , Luo Mao , Chen Ni , Xia Jiyi , Deng Xin , Wu Jianbo 
Published: March 2022

Objective.
Platelets were presented in human atherosclerotic plaque. The function of platelets in the development of atherosclerosis is far poorly defined. We addressed the role of platelets in mediating atherosclerosis formation.

Methods and Results.
Apolipoprotein E-deficient mice (ApoE-/-) were fed with a high-fat Western diet for 12 weeks. Thrombocytopenia was induced by intraperitoneal (i.p.) injections every 3 days with mouse of the platelet-depleting antibody to ApoE-/- mice from 8 weeks. Until the experimental endpoint, atherosclerotic lesion in the aorta and aortic roots were quantified after staining. Size of atherosclerotic plaque in aortic root did not differ between platelet-depleted mice and controls (134±13.1 μm2 [x103] vs 124±11.4 μm2 [x103]; P>0.5). Plasma cholesterol did not differ between groups. However, atherosclerotic lesions of platelet-depleted mice exhibited thinner fibrous caps (62.5±9.2 μm vs. 323±63 μm; P<0.05) and larger necrotic cores (19.5±4.9 μm2 [x103] vs. 4.8±0.8 μm2 [x103]; P<0.05) than controls. Furthermore, compared with controls, platelet-depleted AopE-/- mice promoted significantly increased number of macrophage infiltration into the atherosclerotic lesions.

Conclusion.
Our results suggest that platelet depletion promotes atherosclerotic plaque instability in the development of early atherosclerosis, likely though the macrophage infiltration. These results offer important insights into the in vivo function of platelet, and help to explain the association between enhanced platelet deposition and thrombotic complications of atherosclerosis, such as myocardial infarction.
Abstract 383: Lack of Endogenous Acute Phase Serum Amyloid A Does Not Impact Atherosclerotic Lipid Deposition in ApoE-/- Mice.
Authors: De Beer Maria C , Wroblewski Joanne M , Rateri Debra L , Howatt Deborah , Balakrishnan Anju , Tannock Lisa R , Daugherty Alan , De Beer Frederick C , Webb Nancy R 
Published: March 2022

Inflammation is involved in all stages of the development of an atherosclerotic plaque. Serum amyloid A (SAA), a marker of inflammation, is a well-known predictor of increased cardiovascular risk. Although elevated levels of plasma SAA have been associated with increased atherosclerosis, the role of SAA in the pathogenesis of atherosclerosis remains obscure. To investigate the impact of endogenous SAA in the etiology of atherosclerosis we bred mice lacking both major acute phase SAA isoforms SAA1.1 and SAA2.1 to apoE-/- mice. Both strains were in the C57BL/6 background. For ease of terminology we refer to these mice as SAAKO and apoE-/- mice. Aortic atherosclerotic lesion areas were quantified by en face analysis in male and female mice fed normal chow for 12 months. Although female mice weighed less and had lower plasma lipid levels than male mice, the absence of SAA did not affect plasma lipid concentrations or lipoprotein-cholesterol profiles or the size of aortic atherosclerotic lesions of apoE-/- mice. To accelerate lesion formation, male and female apoE-/- and SAAKO mice were fed a Western diet for 12 weeks. We observed gender-related differences in body weight, weight gain and plasma lipid concentrations. However, absence of SAA in apoE-/- mice fed a diet enriched in saturated fat had no discernable effect on plasma lipid concentrations, lipoprotein-cholesterol profiles or the size of the aortic atherosclerotic lesions. Lesions in the aortic root of male mice, quantitated by oil red O staining, was also not affected by genotype.
We conclude that absence of endogenous acute phase SAA does not impact atherosclerotic lesion development in apoE-/- mice fed normal or fat-enriched diets.
Abstract 390: Perilipin 1 (plin1) Genotype and Not Gpr109a Associated with Free Fatty Acid Rebound Following Niacin Administration
Authors: Tuteja Sony , Dunbar Richard , Qu Liming , Li Mingyao , Mucksavage Megan , DerOhannessian Stephanie , Reilly Muredach , Rader Daniel 
Published: March 2022

Niacin has been used for decades as a lipid lowering agent. Stimulation of a G-protein coupled receptor (GPR109A) on adipocytes by niacin results in the anti-lipolytic effect of the drug and reduction in free fatty acids (FFA), a key pharmacodynamic readout of niacin action. Niacin also causes a subsequent rebound increase in FFA which may be linked to adverse glycemic effects. An evoked phenotype genetic study was undertaken to address the hypothesis that variation in
GPR109A
is associated with the FFA suppression and/or rebound with single-dose niacin.

The study recruited n=294 healthy volunteers (mean age 26 ± 7 years, 51% Female, 35% African-American (AA), 65% Caucasian (Cau)) to an inpatient immediate release 1 gm niacin challenge. The single exon gene
GPR109A
(1092 bp) was sequenced and genotyping was performed on Affymetrix 6.0 genomewide SNP array. Adipose tissue proteomics was performed for 6 subjects comparing pre-post niacin samples (Applied Biomics, Hayward, CA). Serial plasma samples were collected for FFA, insulin, and glucose determination.

The FFA nadir was 0.09 ± 0.08 meq/L, occurred at 2.2 ± 0.7 hr post niacin, and was lower in Cau (0.09 ± 0.08 vs 0.10 ± 0.07, p=0.003). FFA rebound occurred at 4.9 ± 0.7 hr and was lower in AA (1.7 ± 0.5 vs 2.0 ± 0.5, p<0.0001). Fasting insulin levels and HOMA-IR increased 94 ± 106% (p<0.0001) and 96 ± 149% (p<0.0001), respectively at 5 hr compared to baseline. The two common
GPR109A
SNPs, C931T (MAF 0.12) and G951A (MAF 0.31), were not associated with FFA nadir nor rebound. Proteomics analysis of adipose tissue samples revealed increased perilpin1 protein expression two hours after niacin. Cau individuals homozygous for the variant allele for
PLIN1
(
rs894160
) had a lower FFA rebound than those with the wild-type allele (p=0.04).

Summary

Variation in the niacin receptor
GPR109A
was not associated with FFA suppression nor rebound. Using an unbiased proteomics screen, we discovered that niacin increased protein expression of perilipin1, a lipid droplet protein that functions to restrict access of lipases to the triglyceride core. A common non-coding variant in
PLIN1
was asociated with niacin induced FFA rebound. Pharmacogenomics of niacin may serve to identify patients who may be hyper-reponders to niacin therapy.
Abstract 397: Changes in Lipoprotein Subfraction Concentrations After Treatment with the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib Alone or in Combination with Atorvastatin
Authors: Krauss Ronald M , Pinto Cathy Anne , Liu Yang , Johnson-Levonas Amy O , Dansky Hayes M 
Published: March 2022

Background
Anacetrapib (ANA), a cholesteryl ester transfer protein inhibitor, has been shown to increase plasma HDL cholesterol and reduce LDL cholesterol, both as monotherapy and in combination with atorvastatin (ATORVA). The effects of these regimens on lipoprotein subfractions have not been reported.

Methods

ApoB-containing lipoprotein particle subfractions were measured by ion mobility in a post-hoc analysis of baseline and 8 week on-treatment samples from 464 dyslipidemic participants who had been randomized to placebo, ATORVA 20 mg/d, or to ANA at several doses administered with and without ATORVA (
clinicaltrials.gov
NCT00325455
).

Results
ANA (combined 150 mg/d and 300 mg/d groups) significantly reduced total LDL particle concentration by 51%, and levels of large, medium, and small LDL particles (LDL 1, 2, and 3a) by 43-72% but significantly increased levels of the less abundant cholesterol-depleted very small LDL 4a and 4b species by ~64%. In contrast, ATORVA, despite producing a similar reduction of total LDL particle concentration (50%), reduced the levels of all LDL particle subfractions, although the magnitude was smaller for LDL 4a, with a much smaller non-significant reduction for LDL 4b. Compared with ANA monotherapy, results for combination treatment were generally consistent with additive effects. Notably, for individuals with baseline triglyceride (TG) above the median (>154 mg/dL), increases of very small LDL after ANA were markedly attenuated, whereas after ATORVA there was greater reduction of LDL 4a in the higher TG group.

Conclusions
Similar reductions of LDL levels after ANA or ATORVA were not associated with comparable effects on all LDL particle subfractions, and neither drug was effective in lowering levels of the smallest LDL particles. Assessment of the clinical impact of the effects of ANA on LDL subfractions, and the differential changes in very small LDL in individuals with normal versus elevated TG, await cardiovascular outcome data from REVEAL.