bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 314: The Safety of Preoperative Vardenafil in Patients Undergoing Coronary Bypass Surgery.
Authors: Ali Asghar , Binder Andrew , Mohmand Asad , Stewart Helen , Pipkin Margaret , Martin Lisa , Szentpetery Szabolcs , Katlaps Gundars , Jovin Ion S 
Published: March 2022

Objectives
Advances in cardiac surgery have significantly improved the outcomes for patients with myocardial ischemia. However, ischemia/ reperfusion injury represents a mechanism that continues to limit the effectiveness of coronary bypass graft surgery (CABG). Phosphodiesterase 5 inhibitors have been shown to exhibit powerful cardioprotective effects in animal models of ischemia-reperfusion injury. We evaluated the safety of vardenafil in patients undergoing cardiac surgery.

Methods
10 male patients undergoing CABG with or without valve surgery were enrolled in the study. Subjects were given a onetime dose of 10 mg oral vardenafil on the morning of surgery. They were monitored for adverse events and left ventricular ejection fraction changes; pertinent clinical parameters were also recorded. Their postoperative parameters and outcomes were also compared with 47 patients who underwent CABG in the same period of time (control group).

Results
The study drug was tolerated well. There were no episodes of hypotension or deaths in the group receiving vardenafil. The left ventricular ejection fraction did not change significantly after surgery (0.54±0.08 vs 0.53±0.09; P=0.76) in the vardenafil group. The vardenafil group and the control group were similar in terms of clinical characteristics. The type of operation and operative parameters were also similar between the two groups. Peak troponinT levels were not significantly lower in the vardenafil group compared to the control group (9.1 ± 8.3 vs 12.5 ± 9.3 ng/mL; P = 0.26, respectively). The median duration of intubation was not significantly different in the vardenafil group compared to the control group (21.4 ± 10.1 vs 27.4 ± 15.2 h; P = 0.14). The length of hospital stay was also not significantly different between the vardenafil group and the control group (11.1 ± 13.2 vs 10.0 ± 4.7 days; P=0.80, respectively).

Conclusions
Vardenafil is well tolerated when given to patients immediately prior to CABG surgery and appears safe especially in the setting of the intensive care unit where blood pressure and other vital signs are closely monitored. A larger trial is needed to document the cardioprotective effects of the drug in these patients.
Abstract 327: Ankle-Brachial Index is Associated with Subendocardial Viability in Biracial (black-white) Young Adults: The Bogalusa Heart Study.
Authors: Fernández Alonso Camilo , Li Shengxu , Thakkar Badal , Srinivasan Sathanur R , Chen Wei , Blandon Roberto , Berenson Gerald S 
Published: March 2022

Ankle-Brachial Index (ABI) has been widely used clinically to define peripheral artery disease (PAD). Previous studies have established the correlation between ABI and coronary artery disease among men and women; however, limited information is available on the association between ABI and subendocardial viability in terms or Subendocardial Viability Ratio (SEVR) -a measure of myocardial perfusion-, among asymptomatic biracial (black-white) young adults.
We assessed the hypothesis that ABI is directly correlated with SEVR in asymptomatic biracial (black-white) young adults.
As a part of The Bogalusa Heart Study, a bi-racial (black/white) community based study, noninvasive assessment of ABI and SEVR was obtained in 610 asymptomatic individuals aged 29-51years (mean 43.4; 68.7% white and 54.6% female), along with evaluation of traditional cardiovascular risk factors. The association of ABI with SEVR was tested through multivariable-adjusted linear regression.
Black and female participants had significantly lower mean levels of SEVR (p<0.001) and ABI (p<0.001), compared to their counterparts. In race-specific stepwise multiple regression analyses, with adjustments for age, body mass index, sex, smoking status and traditional CV risk factors, significant direct associations were observed between ABI and SEVR in both, white (B=0.25, p<0.001) and black participants (B=0.11, p<0.03), with a stronger association in white participants.
The observed association of ABI with SEVR in black-white asymptomatic adults supports the hypothesis that, structural changes in the peripheral vasculature are reflective of changes in the coronary arteries, even at subclinical level, which may aid to enhance early detection of coronary artery disease in asymptomatic individuals.
Abstract 341: Expression of Leukocyte CD39 in Acute Coronary Syndrome
Authors: Sutton Nadia R , Baek Amy , Liao Hui , Kanthi Yogen , Song Christopher , Visovatti Scott , Pinsky David J 
Published: March 2022

Background
CD39 (ENTPD-1) is a membrane-spanning ectonucleotidase that is responsible for the phosphohydrolysis of ATP to ADP and ADP to AMP. As increased myocardial infarct sizes have been reported in murine CD39 knockout models when compared with controls, we hypothesized that CD39 might be expressed as part of the myocardial injury/repair response. CD39 levels have not been heretofore described in humans with acute coronary syndrome (ACS).

Objectives
To measure CD39 mRNA and protein levels in human study subjects with ACS compared with healthy controls.

Methods
Healthy subjects (n=24), defined as having no history of coronary or peripheral arterial disease, and subjects with ACS (n=13) were enrolled in the study. Blood was collected via venupuncture for healthy controls or at the time of cardiac catheterization for ACS subjects. Plasma and leukocytes were isolated from blood, and soluble CD39 protein from leukocytes was measured using ELISA. mRNA was extracted from leukocytes, and qPCR was used to measure differences in leukocyte CD39 mRNA. Mass spec was used to assess plasma ATP, ADP, AMP, and adenosine levels.

Findings

Increased CD39 mRNA expression was found in subjects with ACS when compared with healthy controls (2.39 vs. 1.66, p=0.021). There was a trend towards increased leukocyte CD39 protein concentrations in ACS patients (n=5) compared to controls (n=9) (7.50 ng/ml vs. 2.64 ng/ml, p=0.057) when measured by ELISA. There was a trend toward increased levels of soluble plasma CD39 levels in ACS patients (n=12) when compared with controls (n=24) (2.39 ng/ml vs. 1.67 ng/ml, p=0.59) when measured by ELISA. ACS patients (n=11) were found to have higher levels of circulating ADP as assessed by Mass spec when compared with healthy controls (n=17), 2.02 vs. 0.67, p=0.03. Leukocyte CD39 levels positively correlated with ATP (r
2
=.231) and ADP (r
2
=.155) levels (n=10).

Conclusions
This is the first report of increased CD39 gene expression in patients with ACS, when compared with healthy controls without known coronary disease. A trend toward increased plasma and leukocyte CD39 protein expression was present in those with ACS when compared with controls. CD39 could serve as a modulator of vascular homeostasis in ACS.
Abstract 361: Characterization of Lipoproteins in the Hypertriglyceridemic Fredrickson-Levy Dyslipidemic Phenotypes with Chylomicrons: The Very Large Database of Lipids (VLDL-7)
Authors: Hassan Kamran , Jones Steven R , Martin Seth S , Joshi Parag S , Blaha Michael J , Elshazly Mohamed , Kulkarni Krishnaji R , Toth Peter P 
Published: March 2022

Background
The major dyslipidemia (DL) classes (I-V) are relatively rare with limited phenotypic characterization across large populations.

Methods
We studied 1,340,614 U.S. adults from the Very Large Database of Lipids and identified those with chylomicron (CM) excess (types I and V). Lipid testing was by ultracentrifugation (VAP, Atherotech, Birmingham, AL). The distributions of total cholesterol (TC), HDL-C, LDL-C and triglycerides (TG) in the database were superimposable with those in the NHANES 2007-2008 survey. We used the following criteria to classify the excess lipoprotein components of DL in subjects with TG >130 mg/dL: CM defined by TG/Total cholesterol (TC) ratio > 9 only (Type I) and CM with >90th percentile VLDL-C (Type V). Subjects with types II, III, or IV DL were excluded.

Results
Type I DL was characterized by very high TG and very low HDL-C, LDLr-C, non-HDL-C and normal VLDL-C and RLP-C. Type V was characterized by TG approximately twice that of type I, low HDL-C and LDLr-C, and elevated VLDL-C, RLP-C and non-HDL-C. The VLDL3-C/IDL-C ratio was approximately 2, twice that of the non-CM groups (Table).

Summary
To our knowledge, this is the largest single report of subjects with these rare hyper-CM phenotypes. The findings support the mechanism of reduced CM clearance and impaired conversion of VLDL to IDL and LDL. The marked reduction in HDL-C is consistent with cholesterol ester transport protein mediated TG-Cholesterol ester exchange between CM and apoB100 lipoproteins.
Abstract 364: Loss Of Systemic C-kit Function Determines Atherosclerosis Burden In Hyperlipidemic Mice
Authors: Song Lei , Duque Juan Camilo , Pena Angela , Shehadeh Lina , Webster Keith A , Pham Si M , Vazquez-Padron Roberto I 
Published: March 2022

Introduction
C-kit is one of the most important tyrosine kinase receptors dynamically regulated in healthy and diseased blood vessels. However, whether c-Kit signaling is beneficial or detrimental to the vasculature remains elusive. This study assesses the impact of the loss of c-Kit in somatic and circulatory cells on atherosclerosis.

Methods and Results

c-Kit expression was abundant in human aortas as determined by RT-PCR, Western blot and immunofluorescence (IF) confocal microscopy. The vascular expression of this receptor varied among patients and tended to decrease in atherosclerotic arteries. Interestingly, in the murine aorta from a c-Kit reporter mouse, GFP was only found in a sub fraction of quiescent VSMC that reside just below the endothelium. c-Kit deficiency favored VSMC proliferation when aortic explants from c-Kit mutant (W/Wv) and wild type (WT) mice were simultaneously placed in a tissue culture system (cells per well: 1337 ± 167 vs. 696 ± 108, p= 0.0123). To measure the contribution of c-Kit signaling to atherosclerosis disease in ApoE KO mice, we fed ApoE KO mice carrying the c-Kit mutant alleles W and Wv with a high-cholesterol diet for 16 weeks. The atherosclerosis plaque burden in these mice was 2.5 greater than in control ApoE KO kit
+/+
mice (affected proportion of the aorta: 0.25 ± 0.03 vs.0.104 ± 0.01, p= 0.0002). Finally, we rescued lethally irradiated ApoE KO W/Wv and control ApoE KO kit
+/+
mice with ApoE KO kit
+/+
bone marrow (BM) cells to determine how the lack of c-Kit activity in BM-derived cells modifies atherosclerosis. While BM transplantation ameliorated most of the hematopoietic defects in the ApoE W/Wv recipients, it had little or no effect on preventing atherosclerotic disease development (affected proportion of the aorta: 0.09 ± 0.01 vs.0.05 ± 0.007, p= 0.03).

Conclusion
Our results demonstrate for the first time that somatic c-Kit-positive cells may confer protection against atherosclerosis in hyperlipidemic mice.
Abstract 367: Macrophage 12/15-lipoxygenase Mediates Insulin-like Growth Factor I (IGF-1)-induced Suppression of Foam Cells: Potential Mechanism Responsible for IGF-1-induced Atheroprotection
Authors: Sukhanov Sergiy , Vaughn Charlotte , Snarski Patricia , Kim Catherine , Delafontaine Patrick 
Published: March 2022

We have shown that IGF-1 infusion into Apoe-null mice suppressed atherosclerosis. To define mechanisms we performed RT-PCR array and found that IGF-1 (0.8 mg/kg, i.p, 7d) reduced aortic 12/15-lipoxygenase (LOX) expression (64±6% decrease vs. saline control, P<0.05). Macrophage LOX is a major pro-atherogenic enzyme that mediates oxidation of native low density lipoprotein (nLDL) and via this mechanism LOX promotes lipid uptake by macrophages (MΦ) and formation of foam cells. IGF-1 infusion into Apoe-null mice (1.5 mg/kg/d, 12 wks on a Western diet) reduced LOX plaque immunopositivity (74±9% decrease, P<0.05), suppressed plaque oxidative stress (64±7% decrease, IHC with 8-oxodG a/b, P<0.05), reduced plaque lipids (35%±6 decrease, Oil Red staining, P<0.05) and decreased atherosclerotic lesion area in aortic valve (IGF-1: 0.259 ± 0.018 mm2, saline: 0.356 ± 0.031 mm2; P<0.05).
To further define mechanisms THP-1-derived MΦ were exposed to IGF-1. IGF-1 (50 ng/ml, 16h) reduced LOX mRNA (49±6% decrease, RT-PCR, P<0.05), decreased LOX protein (42±6% decrease, immunoblotting with LOX a/b, P<0.05) and reduced LOX activity (32±5% decrease, 15S-HETE ELISA, P<0.05) and IGF-1 suppressed STAT6 transcription factor binding to LOX gene promoter region (CHIP assay with STAT6 a/b). IGF-1 markedly reduced oxidation of nLDL mediated by THP-1 or mouse peritoneal MΦ (85±6% and 67±5% decrease, respectively, MDA assay). IGF-1 decreased subsequent LDL uptake (i.e. formation of foam cells) mediated by THP-1 or WT peritoneal MΦ (45±8% and 51±3% decrease, respectively, Oil Red staining); however both lipid uptake and IGF-1 effect were decreased in peritoneal MΦ isolated from LOX-null mice (P>0.05). These data indicate that specific LOX downregulation mediates IGF-1-induced suppression of nLDL oxidation and formation of foam cells. In summary, IGF-1 reduced LOX expression in atherosclerotic plaque and this effect correlated with reduction in plaque lipids and in total atherosclerotic burden. IGF-1 downregulated LOX in cultured MΦ via inhibition of STAT6-dependent transcription and IGF-1 decreased lipid oxidation and uptake by MΦ. Taken together these data strongly suggest that MΦ LOX downregulation mediates IGF-1-induced reduction in foam cells and in atherosclerosis.
Abstract 37: Association between High-Density Lipoprotein Cholesterol Subfractions and Carotid Intima-Media Thickness
Authors: Tiozzo Eduard , Gardener Hannah , Hudson Barry I. , Dong Chaunhui , Weiss Danielle , Della Morte David , Elkind Mitchel S , Disla Norbelina , Wright Clinton B , Sacco Ralph L , Rundek Tatjana 
Published: March 2022

Background
Recent trials have challenged the protective effect of HDL in atherosclerosis, implicating the need to shift the focus from total HDL concentration to its function and major subfractions. The objective of this cross-sectional study was to investigate the relation between HDL2 and HDL3 subfractions and carotid intima-media thickness (IMT), an early indicator of atherosclerosis and surrogate marker of ischemic stroke.

Methods
In NOMAS, a prospective population-based study of the incidence and risk factors of stroke, we evaluated 1041 participants (mean age 68±9 years; 38% men; 62% Hispanic, 19% black, 17% white) with available data on HDL subfractions and carotid IMT assessed by a high-resolution 2D carotid ultrasound. Carotid IMT was a composite measure of the mean IMT in all carotid artery segments. The cross-sectional association between HDL-subfractions and IMT was analyzed by multiple linear regression.

Results
We mean±SD of total HDL was 46.15±14.25 mg/dl (median = 44.00), HDL2 14.59±8.29 mg/dl (median = 13.00), HDL3 31.06±8.32 mg/dl (median = 32.00). The mean IMT was 0.90±0.08 mm. After controlling for demographics, LDL, triglycerides, and cholesterol-lowering medication, a strong association was observed between total HDL (per SD, beta=-0.008, p= 0.01), HDL2 (per SD, beta=-0.006, p=0.03) and HDL3 (per SD, beta=-0.007 p=0.01) in relation to IMT. A significant interaction was observed between diabetes (vs. non-diabetes) and HDL2 in relation to IMT (p=0.01; -0.018mm).

Conclusion
The observed strong independent inverse associations between HDL, HDL2 and HDL3 and carotid IMT. HDL2 was only significantly associated with IMT among individuals with diabetes. These observations show novel evidence for a potential role of HDL2 and HDL3 subfractions, providing the opportunity to develop novel HDL-targeted therapies for the prevention of atherosclerosis.
Abstract 377: Development of a Cell-Based Assay for In Vitro Assessment of Ultrasound Enhanced Bevacizumab Release from Echogenic Liposomes for Delivery into Atherosclerotic Adventitia
Authors: Klegerman Melvin E , Naji Ali K , Golunski Eva , Peng Tao , McPherson David D 
Published: March 2022

Introduction.
Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis, not only in tumor growth, but also in vulnerable atheroma progression. Recent research has indicated that bevacizumab, an anti-cancer monoclonal antibody targeting VEGF, can inhibit atheroma progression. We have developed bevacizumab-loaded echogenic liposomes (BEV-ELIP) as an ultrasound-triggered intrinsically targeted controlled release vehicle for treatment of developing atheroma.

Hypothesis.
PMA-treated human umbilical vein endothelial cell (HUVEC) cultures can serve as a means of optimizing BEV-ELIP inhibition.

Methods.
Bevacizumab (1 μg/ml) was added to 18-hour HUVEC cultures in 96-well plates, followed by 10 nM phorbol 12-myristate 13-acetate (PMA) 4 hours later and incubated for 24 hours. Controls consisted of no PMA, no BEV; no PMA + BEV; and no BEV + PMA. Cells were enumerated using a hemacytometer and tetrazolium dye MTT.

Results.
PMA enhanced cell proliferation by 21-50% relative to control cultures, but bevacizumab treatment of PMA cultures inhibited cell proliferation by 30-55%, to levels lower than no PMA + BEV controls (Fig. 1). Cell proliferative effects were paralleled by both cell-associated and secreted VEGF levels (determined by western blot and ELISA, respectively).

Conclusions.
We have developed an in vitro cell-based assay for testing BEV-ELIP efficacy with and without ultrasound pretreatment, involving addition of a BEV-containing sample before PMA and determining the inhibition of cell proliferation. This allows us to optimize our therapeutic prior to testing in an in vivo developing atheroma model.
Abstract 379: Potential Protective Effects of Semaphorin3A on Macrophage Function
Authors: Heidari Maryam , Ebrahimian Talin , Lemarie Catherine A , Simon David , Rivas Daniel , Vali Hojatollah , Mandato Craig A , Lehoux Stephanie 
Published: March 2022

Semaphorin3A (SEMA3A) is a secreted member of the Semaphorin family, first found to play a role in axon guidance. Recently many studies revealed immune functions for this protein. However, how SEMA3A may regulate monocyte and macrophage functions associated with atherosclerosis is unknown.
An early step in plaque formation is the adhesion of monocytes on activated endothelial cells expressing adhesion molecules. However, we found that 25-100 ng/ml SEMA 3A did not affect the adhesion of monocyes on ICAM-1- or VCAM-1-coated plates. Similarly, stimulation of mouse carotid arteries with SEMA3A in an ex-vivo perfusion system, either administered alone or in conjunction with TNF-α, did not increase adhesiveness of monocytes injected in the intraluminal compartment. Furthermore SEMA3A did not stimulate monocyte migration in a boyden chamber assay. However SEMA3A had significant effects on macrophages, the most abundant cells in the plaque. Inefficient apoptotic cell phagocytosis and macrophage retention in the artery wall are hallmarks of atherosclerosis progression. We found that SEMA3A increased the migration of M2 “wound healing” macrophages more than 4-fold (p<0.05), but had no such effect on M1 “inflammatory” macrophages. Increased M2 migration was associated with phosphorylation of FAK Y397, and could be inhibited by RGD peptide that prevents integrin-matrix interaction and by a blocking antibody targeting the SEMA3A receptor Neuropilin-1. SEMA3A (100ng/ml) also significantly increased phagocytosis of apoptotic cells by M2 macrophages (1.8-fold, p<0.01) but not M1 cells. Interestingly, Sema3A did not affect lipoprotein uptake by macrophages, which characterizes foam cell formation. Finally in an in vivo model of acute inflammation, SEMA3A plasmid pretreatment reduced redness, swelling, and macrophage infiltration associated with LPS injection.In summary, our data suggest that SEMA3A is unlikely to participate in atherosclerotic plaque formation. On the contrary, effects of SEMA3A on macrophage function in vitro and in vivo indicate a potential protective effect in the inflammatory setting.
Abstract 386: Air Pollutants Induce Dysfunctional Prooxidant HDL and Activate 5-lipoxygenase in the Liver
Authors: Yin Fen , Lawal Akeem , Ricks Jerry , Fox Julie R , Larson Tim , Navab Mohamad , Fogelman Alan , Rosenfeld Michael , Araujo Jesus A 
Published: March 2022

Background
Exposure to ambient particulate matter is associated with increased cardiovascular ischemic events and enhanced atherosclerosis.

Objective
To test our hypothesis that air pollutants may induce oxidative modifications of plasma lipoproteins resulting in alteration of the anti-oxidant and anti-inflammatory properties of high-density lipoproteins (HDL).

Methods and Results
We exposed ApoE-/- male mice (C57BL/6 background) to diesel exhaust (DE) emissions at 250 μg PM2.5/m3 for two weeks, filtered air (FA) for two weeks or DE for two weeks, followed by FA for one week (DE+FA). HDL anti-oxidant capacity was assessed by a DCF-based cell fluorescence assay that evaluate the ability of HDL to inhibit LDL oxidation. DE and DE+FA mice significantly impaired the HDL anti-oxidant capacity in comparison with FA mice (p<0.001), as judged by almost a doubling in the level of DCF fluorescence and by a promotion rather than inhibition of oxidation. Decreased HDL anti-oxidant properties were accompanied by reduced anti-inflammatory capacity. The HDL anti-oxidant dysfunction correlated with decreased paraoxonase enzymatic activity, increased levels of plasma 8-isoprostanes, 12-HETE, and 13-HODE. DE also led to increased hepatic levels of ALOX5 mRNA and protein, Glutathione Peroxidase 6 mRNA and 5-HETEs, indicating activation of the 5-lipoxygenase pathway in the liver. Moreover, DE led to enhanced lipid peroxidation in the bronchoalveolar lavage fluid as well.

Conclusions
DE emissions induced systemic pro-oxidant effects that led to the development of dysfunctional HDL, which might be one of the mechanisms how air pollution contributes to enhanced atherosclerosis
Abstract 401: Relative Population Percentiles of LDL Cholesterol, Non-HDL Cholesterol and Total Cholesterol to HDL Cholesterol Ratio: The Very Large Database of Lipids Study (VLDL-2)
Authors: Elshazly Mohamed B , Martin Seth S , Joshi Parag H , Blaha Michael J , Kulkarni Krishnaji R , Jones Steven R 
Published: March 2022

Background
Non-HDL cholesterol (non-HDL-C) and the total cholesterol to HDL cholesterol ratio (TC/HDL-C) are alternatives to LDL cholesterol (LDL-C) in risk assessment and decision-making for lipid-lowering therapy.

Methods
We assigned population percentiles to non-HDL-C, TC/HDL-C and LDL-C in 1,340,614 U.S. adults from the Very Large Database of Lipids (VLDL). The distributions of TC, HDL-C, LDL-C and TG in the VLDL were nearly identical to those in the NHANES 2007-2008 survey. Lipids were measured by ultracentrifugation (Atherotech; Birmingham, AL). LDL-C was estimated by the Friedewald method, excluding patients with TG ≥400 mg/dL (2.3% of sample). We examined the relative values of these lipid markers across equivalent population percentiles.

Results

Spearman correlation (ρ) between non-HDL-C and LDL-C percentiles was high overall, ρ=0.94 but lower in patients with LDL-C <70 mg/dL, ρ=0.51; similar for TC/HDL-C and LDL-C percentiles, ρ=0.56; lower in patients with LDL-C<70 mg/dL ρ=0.13. The equivalent non-HDL-C percentile to LDL-C of 70 mg/dL was 93 mg/dL (guidelines recommend 100 mg/dL); equivalent TC/HDL-C of 2.6, the 15
th
percentile. Similarly, the equivalent non-HDL-C percentile to LDL-C of 100 mg/dL was 125 mg/dL (guidelines recommend 130 mg/dL); equivalent TC/HDL-C of 3.3, the 44th percentile (Table).

Conclusion
Selection of treatment targets based on consistent population percentiles may have implications in risk stratification and selection of guideline target values.