bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 405: Therapeutic Potential of Oscimum Tenuiflorum in Prevention and Treatment of Atherosclerosis
Authors: Aluganti Narasimhulu Chandrakala , Vardhan Sangamithra , Parthasarathy Sampath 
Published: March 2022

Background
Current experimental and clinical studies show that Oscimum tenuiflorum (commonly known as basil or Tulsi) possess many health benefits. Oscimum is also suggested to be anti-oxidative and anti-inflammatory. Eugenol, an ortho-methoxy phenol, is one of its components. Myeloperoxidase (MPO), an oxidative enzyme, has been implicated in the pathogenesis of atherosclerosis. MPO dependent oxidation of lipoproteins has been implicated in foam cell formation, dysfunctional HDL and abnormalities in reverse cholesterol transport (RCT). In this study we tested whether eugenol and basil extract could inhibit the oxidation of lipoproteins (LDL & HDL) by MPO.

Hypothesis
Whole leaf extract of Ocimum tenuiflorum and eugenol would inhibit the oxidation of LDL and HDL by myeloperoxidase and by copper.

Methods
Basil leaf extract was prepared with water, lyophilized and reconstituted in water. Lipoproteins (LDL & HDL) were isolated from human plasma and their oxidation was performed using copper or MPO in the presence or absence of the basil extract and eugenol. MPO activity was measured using guaiacol and TMB as substrates.

Results
Basil extract and eugenol inhibited MPO enzyme activity against synthetic substrates. In addition, they also inhibited the oxidation of LDL and HDL both by copper and MPO, as measured by conjugated diene formation, TBARS formation, as well as by electrophoretic mobility assays.

Conclusion
In lieu of the reported anti-inflammatory properties of basil leaves, and the importance of oxidative and inflammatory pathways in atherosclerosis, such simple non-pharmacological agents could prove to be valuable adjunt therapeutic agents in the treatment of cardiovascular diseases.
Abstract 407: Use of Micellarized Cholesteryl Ester to Generate Macrophage Foam Cells
Authors: Sengupta Bhaswati , Aluganti Narasimhulu Chandrakala , Parthasarathy Sampath 
Published: March 2022

Background
Development of foam cells for Reverse Cholesterol Transport (RCT) studies uses the technique of receptor dependent macrophage loading with radiolabeled acetylated LDL. For various reasons this technique is tedious, less reliable and less reproducible. Our goal is to develop foam cells loaded Cholesteryl Ester (CE) in a receptor independent manner and facile manner.

Methods
We micellarized highly nonpolar Cholesterol or CE in aqueous solution of Lyso phosphatidylcholine (Lyso PtdCho) to generate mixed micelles. RAW 264.7 macrophages and mouse peritoneal macrophages were incubated with Cholesterol or CE (unlabeled and fluorescently labeled-NBD cholesterol)/ Lyso PtdCho mixed micelles. The presence of fluorescent Cholesterol and CE was documented by fluorescence microscopy. Foam cell macrophages were detected by Oil-red O staining.

Results
In the presence of Lyso PtdCho, Cholesterol or CE readily formed mixed micelles, generating a clear solution in a concentration-dependent manner. Incubation of Cholesterol or CE rich micelles with macrophages resulted in the uptake of these micelles as noted by fluorescence and Oil-red O staining.

Conclusions
Foam cells developed by this technique could be used for RCT studies. This technique can be manipulated to enrich cells in vitro with various non-polar molecules and could be used to develop different cell based assays.
Abstract 415: Lipid Profiles in Minority and Non-Minority Veterans following Percutaneous Coronary Intervention
Authors: Siddiqui Saifullah , Blumenkrants Dmitry , Ladani Amit , Challa Karthic , Shroff Adhir 
Published: March 2022

Background
Lipid lowering therapy is an established core measure of secondary prevention in coronary artery disease management. The National Cholesterol Education Program - Adult treatment panel III (NCEP ATPIII) guidelines recommend a goal low density lipoprotein (LDL) level less than 100 mg/dL for CAD management. Statins remain the preferred agent for LDL reduction. It is unclear whether race plays a role in lipid control.

Methods
We conducted a retrospective, observational study on all patients undergoing PCI at an urban veterans hospital from September 2004 to December 2011. Statin use and lipid profiles at six months post-PCI were compared to pre-PCI values between minorities and non-minorities.

Results
A total of 1052 patients (60% minorities of which 88% were African American) were analyzed. The mean LDL decreased at six-month follow up in both groups. The mean LDL decreased by 15.2 mg/dL in the minority group and by 15.1 mg/dL in the non-minority group (p<0.0001). The percentage of patients at LDL goals of <100 mg/dL pre-PCI and at six month follow-up increased from 56% to 74% in the minority group (p<0.0001), respectively, and from 64% to 78% in the non-minority group (p=0.0002), respectively. The percentage of patients on a statin pre-PCI and at six-month follow up increased from 69% to 90% in the minority group (p<0.0001), respectively, and 72% to 86% in the non-minority group (p<0.0001), respectively.

Conclusion
Both groups exhibited an improvement in LDL levels six months after PCI and while on statin therapy. The mean difference was equivalent for minorities and non-minorities. This improvement was also reflected in the increased proportion of patients meeting ATPIII guidelines in both groups. There was also an increase in the usage of statin therapy in both groups at six months; however, the minority subgroup displayed a greater increase in statin use when compared to the non-minority subgroup.
Abstract 416: Baseline Electrocardiographic Findings Are Associated With Insulin Sensitivity and Beta-Cell Function in Type 2 Diabetes
Authors: Bhatt Anish B , Mulvey Claire K , Qasim Atif N , Rickels Michael R , Nair Jayamohan , Reilly Muredach P 
Published: March 2022

Introduction
Cardiovascular disease rates are higher in type II diabetes mellitus, but often it remains silent until too late. It is unknown if baseline EKG changes are associated with the degree of impaired insulin sensitivity or with other markers of diabetes control. We sought to investigate these relationships in the Penn Diabetes Heart Study (PDHS), a cross-sectional study of diabetic patients without overt coronary artery disease.

Methods
EKG intervals were measured in a subset of PDHS participants (n=732; mean age 59.4 ± 8.4 years, 66.5% males, 60.1% Caucasians). At the same visit, subjects underwent 75 g oral glucose tolerance testing after overnight fast with measurement of glucose and insulin at 0, 30, 60, and 120 minutes. The Matsuda Insulin Sensitivity Index (MISI) was calculated to estimate insulin sensitivity and the Insulinogenic Index (IGI) to estimate pancreatic beta-cell function. We used spearman correlations, chi-squared tests, and logistic regression to test associations of EKG changes with clinical factors, log-transformed MISI, and inverse normal-transformed IGI.

Results
In unadjusted analysis, there was a higher prevalence of left ventricular hypertrophy (LVH) (3.6% vs. 0.9%, p = 0.005) and ST changes (24.5% vs. 14.6%, p = 0.004) in African Americans compared to Caucasians. In fully adjusted models controlling for age, race, sex, history of hypertension and Framingham risk score, a higher MISI was associated with lower incidence of Q waves (OR 0.50, CI 0.33-0.76, p = 0.001). In addition, higher IGI scores were associated with a lower incidence of nonspecific ST changes (OR 0.82, CI 0.65-0.96, p= 0.035). There was also a trend for higher HbA1c values associated with LVH; however, this association was not statistically significant in fully adjusted models (OR 1.29, CI 0.90-1.86, p = 0.163).

Conclusion
Q wave abnormalities on routine EKGs were associated with reduced insulin sensitivity at baseline, while nonspecific ST changes were associated with lower pancreatic beta-cell function in patients with diabetes. Specific baseline EKG changes are indicators of the degree of metabolic disturbance in type 2 diabetes and may provide insight into the extent and risk of macrovascular and microvascular complications in diabetic patients.
Abstract 421: Anti-Atherosclerotic Effect of Ellagic Acid
Authors: Rani Uma P , Kesavana Rushendhiran , Ganugula Raghu , T Avaneesh , Reddy Bhanuprakash G , Dixit Madhulika 
Published: March 2022

Introduction

Abnormal proliferation and migration of medial vascular smooth muscle cells (VSMC) of vessel wall result in atherosclerotic plaque growth. Targeting proliferation of VSMC could reduce atherosclerotic complications. Therefore, the objective was to study the anti-proliferative effect of Ellagic acid (EA) on primary rat aortic smooth muscle cells (RASMCs) against an atherogenic agonist PDGF
in vitro
and also anti atherosclerotic effect in streptozotocin (STZ) induced diabetic rats.

Methods

Proliferation of cells was measured via Alamar blue assay and through propidium iodide based cell cycle analysis in flow cytometer. Reactive oxygen species (ROS) were measured via 2’, 7’-dichlorofluorescin diacetate (DCF-2DA) and Amplex red methods. Expression of proliferation markers and activation of kinases were assessed by immunoblot analysis. Immunohistochemistry was done on aortic tissue sections obtained from
in vivo
experiments.

Results
Co-treatment of primary cultures of RASMCs with 25μmol/L of EA significantly reduced PDGF-BB (20ng/ml) induced proliferation by blocking S-phase entry. EA effectively blocked PDGF receptor-β (PDGFR-β) tyrosine phosphorylation, intracellular ROS and downstream activation of extra cellular signal-regulated kinase 1/2. It also blocked PDGF-BB induced expression of cyclin D1. Docking analysis with AutoDock4 revealed two binding pockets for EA in the PDGF-BB-PDGFR-β complex with predicted free energy of bindings similar to known inhibitor, AG1295. In diabetic rats, supplementation of diet with 2% EA significantly blocked diabetes-induced medial thickness, and lipid and collagen deposition in the arch of aorta as well as proliferation marker cyclin D1 expression.

Conclusion
Therefore, EA is effective as anti atherogenic nutrient therapy.
Abstract 427: Apoliporotein A-I Improves Glucose Tolerance and Enhances Insulin-Dependent and Insulin-Independent Glucose Uptake in the db/db Mouse Model of Type 2 Diabetes
Authors: Cochran Blake J , Tang Shudi , Rye Kerry-Anne 
Published: March 2022

Introduction
Type 2 diabetes is characterised by decreased high-density lipoprotein (HDL) levels, as well as the level of apolipoprotein A-I (apoA-I), the main apolipoprotein of HDL. Pharmacological elevation of HDL levels is associated with improved glycemic control in patients with type 2 diabetes and HDL also improves glucose uptake into skeletal muscle in vitro. With the current interest in HDL raising therapeutics, understanding how apoA-I/HDL improve glucose tolerance in type 2 diabetes is important.

Objective
To determine the impact of increasing plasma apoA-I levels on glycemic control and glucose uptake in the db/db mouse model of type 2 diabetes.

Methods
Fasted 6-7 week old male db/db mice received a single intraperitoneal injection of human apoA-I (40 mg/kg) or PBS. Two hours after the infusion mice were randomly assigned into 3 groups (n=7-8/group) and subjected to a glucose tolerance test (1 g/kg D-glucose), an insulin tolerance test (3 U/kg human insulin) or used to determine glucose uptake into skeletal muscle. For the glucose and insulin tolerance tests blood glucose levels were measured with a glucometer. For the glucose uptake experiments, gastrocnemius muscles were incubated with 1 mM [3H]2-deoxy-glucose and 7 mM D-[14C]mannitol in the presence or absence of insulin, then homogenized. 3H and 14C content of the homogenates was determined by liquid scintillation counting.

Results
Plasma apoA-I levels reached 65.2±16.6 μg/mL by 2 h post-injection, and remained elevated for >10 h. Mice that received apoA-I had significantly improved glucose tolerance (AUC apoA-I=2574±70; PBS=2927±137, p<0.05) and insulin sensitivity (AUC apoA-I=388.8±23.8; PBS=194.1±19.6, p<0.001). In the absence of insulin, apoA-I increased glucose uptake by 1.8 and 1.7 fold in red and white gastrocnemius muscle, respectively. In the presence of insulin, apoA-I increased glucose uptake 2.5 and 1.8 fold, in red and white gastrocnemius muscle, respectively.

Conclusion
A single infusion of apoA-I significantly increases glucose tolerance, insulin sensitivity and skeletal muscle glucose uptake in db/db mice. Insulin and apoA-I work synergistically to improve skeletal muscle glucose uptake.
Abstract 446: Therapeutic Silencing of MicroRna-33 In Mice Inhibits the Progression of Atherosclerosis in Ldlr-/- Mice
Authors: Rotllan Noemi , Ramírez Cristina M , Esau Christine C , Fernández-Hernando Carlos 
Published: March 2022

Objective-
To study the efficacy of anti-miRNA-33 therapy on the progression of atherosclerosis.

Methods and Results-

LDLr
-/-

mice were injected subcutaneously with PBS, control or miR-33 antisense oligonucleotides (ASO) weekly and fed a Western diet for 12 weeks. As expected, hepatic levels of miR-33 were significantly decreased in anti-miR-33 treated mice. Accordingly, the expression of miR-33 target genes was increased in the liver and aorta. Interestingly, plasma HDL cholesterol (HDL-C) was significantly increased in anti-miR-33 treated mice but only when they were fed a chow diet. Analysis of atherosclerosis revealed a significant reduction of plaque size and macrophage content in mice receiving miR-33 ASO. In contrast, no differences in collagen content and necrotic areas were observed between the three groups.

Conclusions-
Long-term anti-miR-33 therapy significantly reduces the progression of atherosclerosis. The miR-33 ASO anti-atherogenic effect is independent of plasma HDL-C.
Abstract 448: The Association of 5A Peptide With Sphingomyelin Increases Its Ability to Efflux Cholesterol Both in vitro and in vivo
Authors: Sviridov Denis O , Schwendeman Anna A , Kim Gwangseong , Stonik John , Turner Scott , Remaley Alan T 
Published: March 2022

Introduction
5A (DWLKAFYDKVAEKLKEAF-P-DWAKAAYDKAAEKAKEAA) is an apolipoprotein A-I mimetic peptide that is specific for promoting cholesterol efflux by the ABCA1 transporter and has been shown to reduce atherosclerosis and inflammation in animal models.

Hypothesis
In this study, we complexed the 5A peptide with sphingomyelin (SM) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) to compare the cholesterol efflux capacity of the complex and its affect on atherosclerosis.

Results
The optimal peptide to lipid ratio was found to be 1 to 7 (mole/mole) for both lipids. The average particle size measured by light scattering technique was 15.9 ± 2.2 nm for 5A-SM complex and 14.4 ± 3.5 nm for 5A-POPC complex. 5A-SM exhibited higher physical binding of fluorescently labeled cholesterol relative to 5A-POPC with Bmax of 182.6 ± 14.4 versus 124.8 ± 8.2, respectively. In the cholesterol efflux assay (18h), both complexes showed near equal efflux capacity through ABCA-1 transporter (25.4 ± 1.2 efflux for 5A-SM and 23.0 ± 0.2 % efflux for 5A-POPC). Interestingly, 5A-SM showed significantly higher cholesterol efflux in ABCG-1 and SR-B1 transfected cell lines compere to 5A-POPC (42.7 ± 1.8% vs. 29.1 ± 0.6 and 29.0 ± 2.4% vs. 13.3 ± 0.2%, respectively). Lipid free 5A peptide showed lower cholesterol efflux through ABCA-1 transporter (15.8 ± 1.2%) and showed no efflux through ABCG-1 or SR-B1. The abilities of the peptide-lipid complexes to mobilize cholesterol in vivo were tested on wild type rats. Two hours after intravenous injection of 100 mg/kg 5A-SM plasma cholesterol increased about 3-fold above baseline with a peak at 6 hours and returned to the baseline by 24 hours. 5A-POPC increased plasma cholesterol 2-fold above and returned to baseline by 24 hours.

Conclusions
The 5A complexed with SM showed similar ability to efflux cholesterol by ABCA1 than the 5A-POPC complex but improved cholesterol efflux capacity by ABCG1 and SR-BI. A greater rise in HDL-C was observed in vivo after treatment of rats with 5A-SM versus 5A-POPC, suggesting that the 5A-SM complex may show superior ability in increasing Reverse Cholesterol Transport and in reducing atherosclerosis, which will be examined in future studies.
Abstract 454: Cationic Peptides Neutralize Ox-LDL and Acetyl LDL Negative Charge and Prevent Their Uptake by Macrophages
Authors: Aluganti Narasimhulu Chandrakala , Brown Matt , Selvarajan Krithika , Parthasarathy Sampath 
Published: March 2022

Background
Apoprotein (Apo A1) and apoprotein E mimetic peptides are known to reduce atherosclerosis. Antioxidant, anti-inflammatory, and hypolipidemic properties have been suggested to contribute to the anti-atherosclerotic effects. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins and inhibit their uptake by macrophages.

Methods
5F-mimetic peptide of apoA1, LL27 derived from the anti-microbial peptide CAMP, and a human glycodelin derived peptide were commercially synthesized. The number of positively charged amino acid residues (K+R) and negatively charged residues (D+E) were 4/4, 7/4, 6/2 respectively. Their abilities to reduce lipid peroxides (LOOH), inhibit the oxidation low density lipoprotein (LDL) and high density lipoprotein (HDL), interact with modified lipoproteins, and to inhibit macrophage uptake of modified LDL were measured.

Results
Cationic peptides decomposed the peroxide content of 13-HPODE and inhibited the oxidation of LDL and HDL by copper in a lysine dependent manner. Incubation of Ox-LDL and Ac-LDL with the peptides resulted in charge neutralization as noted by agarose gel electrophoresis. Pre-incubation of the peptides with modified lipoproteins reduced the uptake of the latter by macrophages and foam cell formation as detected by Oil-Red O staining.

Conclusions
Based on these studies, we postulate that cationic peptides may have properties that may affect a) events that are unrelated to lipid lowering, b) may play additional role in immune competent cells, including macrophages, and c) may interact with other biologically important anionic molecules, including lipids and proteins. These results also suggest there may be other cationic proteins that may influence the atherogenic processes.
Abstract 459: Noninvasive Measures of Arterial Stiffness in a Young Normotensive/Prehypertensive Patient Population
Authors: Cheng Cynthia , Daskalakis Constantine 
Published: March 2022

Introduction
Noninvasive measures of atherosclerosis have become established tools for cardiovascular risk prediction, largely studied in older individuals. Pulse pressure (PP) is a simple surrogate measure of arterial stiffness, while Ambulatory Arterial Stiffness Index (AASI) is a relatively new vascular compliance measure calculated as 1 minus the regression slope of DBP over SBP readings obtained from 24 hour ambulatory blood pressure monitoring (ABPM). We examined the hypothesis: PP and AASI correlate with blood pressure (BP), along with microvascular and endothelial function, in young adult normotensive and prehypertensive subjects.

Methods
24 hour BP, PP, and AASI were calculated from ABPM, and clinic BP obtained in 140 subjects (87 female, 53 male; 117 non-black, 23 black) with mean +/- sd age 26 +/- 6 years. Strain gauge plethysmography was used to assess endothelial function. Microvascular function was measured with direct capillaroscopy visualization of capillaries. Pearson correlation coefficients and multiple linear regression were used to analyze BP, microvascular, and endothelial function as predictors of PP and AASI, controlling for BMI, gender, age and race.

Results
PP and AASI are correlated (r=0.59; p<0.001). Both PP and AASI were significantly associated with ABPM and clinic SBP measures (SBP24: p=0.001/p=0.002; SBP daytime: p=0.001/p=0.009; SBP clinic: p=0.001/p=0.047; p values =PP/AASI). No association was seen for any measures with DBP. Both PP (p=0.08) and AASI (p=0.056) were marginally associated with endothelial function, while only AASI was significantly associated with microvascular function (p=0.027) along with BP dipping (drop of 10% or more during sleep: SBP and DBP p<0.001), another known predictor of cardiovascular risk.

Conclusions
In conclusion, both PP and AASI are associated with SBP in young normotensive and prehypertensive patients, indicating potential usefulness of these measures for early identification of arterial stiffness and associated cardiovascular risk, prior to development of established hypertension. Microvascular and endothelial dysfunction may contribute to the pathophysiology underlying higher PP/AASI values, with AASI more closely correlated with these processes.
Abstract 461: Inhibition of Four- and- a- Half LIM Domain Protein-2 Decreases Atherosclerosis in Apoe -/- Mice model: Role of Immune T- Cells
Authors: Ebrahimian Talin , Heidari Maryam , Lemarie Catherine A , Simon David , Rivas Daniel , Mann Koren , Wassmann Sven , Lehoux Stephanie 
Published: March 2022

OBJECTIVE
Four-and-a-half LIM domain protein-2 (FHL2), a member of the FHL family of proteins, is expressed in endothelial and vascular smooth muscle cells. FHL2 negatively regulates endothelial cell survival and migration, but its role in atherogenesis is unknown.

METHODS AND RESULTS

To investigate the role of FHL2 in atherosclerosis, we crossed FHL2 knockout (FHL2-/-) with apolipoprotein (Apo) E-deficient (ApoE -/-) mice, and fed them a high fat diet for 7 weeks. Despite a total plasma cholesterol levels comparable to the ApoE-/- mice, FHL2-/-ApoE-/- mice showed a strong increase in plasma HDL-cholesterol as compared to ApoE -/- mice (P<0.01; n=6) and had significantly smaller atherosclerotic plaques in the aortic sinus (0.14±0.02 vs. 0.29±0.04 mm
2
) and aorta (6.9±0.9 vs 10.3±1%) (P<0.05; n=6), assessed by oil red O staining, compared with ApoE-/- mice. The relative monocyte/ macrophage content within atherosclerotic plaques, determined by MOMA-2 immunostaining, was equivalent in both animal groups. However, we observed an enhanced relative content of collagen (16±2 vs 8.6±3 %) and smooth muscle cells (4.5±0.8 vs 1.8±0.5%) within the plaques in the aortic sinus of FHL2-/-ApoE-/- mice compared with ApoE-/- mice, determined by Sirius red and alpha-actin staining respectively. These results suggest that absence of FHL2 promotes smaller and more stable plaques. The reduced plaque size in FHL2-/-ApoE-/- mice could be explained, at least in part, by the 40% reduction in ICAM-1 mRNA expression observed in aortas (p<0.05 vs ApoE-/-). Moreover, although the relative monocyte/ macrophage content in spleens was equivalent in both animal groups, FACS analysis of T cells in spleens showed a significant increase in CD4+CD25+Foxp3+ regulatory T cell numbers, in FHL2-/-ApoE-/- compared with ApoE-/- mice (19.5±1.6 vs. 16.2±2% of CD3+CD4+ cells, respectively) (P<0.005).

CONCLUSIONS
These results suggest that FHL2 may play an important role in atherosclerosis by promoting plaque formation, through upregulation of adhesion molecule expression and suppression of regulatory T cells.