bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 40: Neutrophil Serine Protease PR3 Promotes Platelet Adhesion and Activation on von Willebrand Factor (vWF) Expressing Endothelial Cells
Authors: Kuckleburg Christopher J , Newman Peter J 
Published: March 2022

Introduction
Neutrophils play important roles in inflammation, regulating vascular permeability and promoting thrombus formation. Upon activation, neutrophils release serine proteases that can activate coagulation factors and protease activated receptors (PARs). Proteinase 3 (PR3) is the most abundant serine protease in neutrophils; however, the role of PR3 in regulating vascular function and thrombosis is not clear. In this study we have used flow chamber assays and confocal microscopy to investigate PR3 activation of endothelial cells through PAR-2 and the recruitment and activation of platelets and leukocytes under shear conditions.

Results
After endothelial cells were incubated with PR3 or a PAR-2 activating peptide, we observed significant release and surface presentation of von Willebrand (vWF) compared to untreated cells. In addition, we also found that PR3 increased endothelial cell adhesion molecule expression and ERK phosphorylation. Using flow chamber assays, we observed that PR3-treated endothelial cells expressing vWF were able to capture platelets from whole blood under venous shear conditions; however, blocking antibodies against either platelet GpIb or GpIIb/IIIa significantly reduced platelet adhesion. Using whole blood, we also found that significant numbers of leukocytes were recruited to PR3-treated endothelial cells. However, in platelet-depleted whole blood, or blood treated with antibodies against GpIb or GpIIb/IIIa, we observed a dramatic reduction in leukocyte adhesion. Therefore, leukocyte recruitment to PR3-treated endothelial cells required platelet activation and adhesion and this was mediated in part by vWF.

Conclusions

Neutrophil PR3 can promote platelet adhesion to the vascular endothelium through a process requiring endothelial cell vWF, platelet GpIb and GpIIb/IIIa. PR3 also promotes leukocyte recruitment to the endothelium through a platelet-dependant process. This data demonstrates that PR3 can be a significant contributor to thrombus formation and leukocyte recruitment to the vascular endothelium and PR3 may be an important target for disrupting thrombus formation
in vivo
.
Abstract 426: Selective Proteolysis of Apolipoprotein A-I by Secretory Phospholipase A2: New Insights Into sPLA2-dependent Catabolism of HDL
Authors: Jayaraman Shobini 
Published: March 2022

Introduction
Secretory phospholipase A2 (sPLA2) is a pro-inflammatory enzyme that promotes atherogenesis via several mechanisms. One of these mechanisms probably involves high-density lipoproteins (HDL). Previous in vitro studies of HDL modified by sPLA2 showed increased exposure of certain domains of the major HDL protein, apoA-I, without protein fragmentation. Over-expression of sPLA2 in transgenic mice reduced plasma levels of HDL cholesterol due to rapid HDL catabolism. The origin of this enhanced HDL catabolism is unknown.

Hypothesis
In addition to hydrolysis of HDL phospholipids, sPLA2 can also hydrolyze apoA-I, leading to enhanced catabolism of sPLA2 modified HDL.

Methods
Human plasma HDL and lipid-free apoA-I were incubated with sPLA2 at 37 oC. The HDL lipids were removed, and the protein integrity was analyzed by gel electrophoresis and mass spectrometry.

Results
Consistent with previous studies, HDL hydrolysis by sPLA2 slightly reduced the particle size without release of protein. SDS PAGE of hydrolyzed HDL showed no significant changes in the protein composition. Interestingly, delipidation of sPLA2-hydrolyzed HDL showed that nearly 10% of apoA-I formed well-defined fragments of 6-15 kDa. Incubation of sPLA2 with lipid-free apoA-I produces very similar fragments, indicating direct action of sPLA2 on apoA-I. Similar incubation of sPLA2 with other HDL proteins, apoA-II and apoC-I, did not lead to proteolysis, indicating enzymatic specificity of sPLA2 for apoA-I. ApoA-I hydrolysis by sPLA2 was Ca-independent and hence, occurred via a different mechanism than the phospholipid hydrolysis by sPLA2 that is Ca-dependent. Mass spectrometry analysis of isolated proteolytic fragments indicated several N-and C-terminal fragments of apoA-I, suggesting at least two cleavage sites in the central domain of apoA-I.

Conclusion
We have identified a previously unknown proteolytic activity of sPLA2 which is specific to apoA-I and is independent of the apoA-I lipidation. This novel enzymatic activity of sPLA2 helps explain enhanced catabolism of HDL in vivo, and is expected to contribute to the pro-atherogenic action of this pro-inflammatory enzyme.
Abstract 440: Non-HDL Cholesterol, Guideline Targets, and Population Percentiles: The Very Large Database of Lipids (VLDL-2 Study)
Authors: Elshazly Mohamed B , Martin Seth S , Joshi Parag H , Blaha Michael J , Kulkarni Krishnaji R , Jones Steven R 
Published: March 2022

Background
Worldwide guidelines recommend a Non-HDL-C target of <100 mg/dL (30 mg/dL above LDL-C target) in high risk patients only when triglycerides (TG) ≥200 mg/dL, although TG of 100 mg/dL is considered “optimal” and TG 150-200 mg/dL is considered “elevated”. The performance of the present guidelines-based TG criterion in identifying treatable dyslipidemia is largely unknown.

Methods
We examined 1,340,614 U.S. adults in the Very Large Database of Lipids (VLDL). Lipid testing was performed 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 calculated the proportion of individuals reclassified using a population percentile based Non-HDL-C target versus the recommended target of <100 mg/dL.

Results
The equivalent Non-HDL-C percentile to LDL-C of 70 mg/dL was 93 mg/dL. In those with LDL-C <70 mg/dL, 15% had a Non-HDL-C≥100 mg/dL while 30% had a Non-HDL-C≥90 mg/dL. Considerable reclassification occurred at TG levels of 100-199 mg/dL.

Conclusion
If a population percentile based Non-HDL-C target of 90 mg/dL were used instead of the guideline mandated 100 mg/dL, twice as many patients with LDL-C <70 mg/dL would be eligible for treatment, including a considerable proportion of patients with TG <200mg/dL. More generalized use of population percentile based Non-HDL-C targets may be superior for secondary prevention at TG levels <200 mg/dL, with implications for guideline development.
Abstract 441: Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) is Elevated in Acute Coronary Syndromes and Resides Predominantly in LDL
Authors: Jabor Bashar , Choi Hong , Ruel Isabelle , Hafiane Anouar , Genest Jacques 
Published: March 2022

Lipoprotein associated phospholipase A2 (Lp-PLA2) may play a role in the formation of vulnerable atherosclerotic plaques and plaque rupture. Its plasma distribution and mass in subjects with acute coronary syndromes (ACS) are not characterized.
The objective of this study was to examine plasma levels and distribution of Lp-PLA2 in patient with ACS.
We compared plasma levels of LP-PLA2 in 23 patients within 48 hours of presentation of an ACS (visit 1) and 12 weeks after (visit 2), in 24 patients with chronic, stable coronary artery disease (sCAD) and in normal healthy controls. The distribution of Lp-PLA2 was determined by ultracentrifugation (UTC), high-performance liquid chromatography (HPLC), and polyethylene glycol (PEG) precipitation of plasma lipoproteins and immunoblotting analysis. Lp-PLA2 mass was determined by ELISA
The ACS patients (18 males/5 females, mean age 57±9.2) had hsCRP levels of 32.6±60.4 mg/L (ACS visit1) vs. 1.9±1.3 mg/L (ACS visit2), reflecting systemic inflammation. Stable CAD hsCRP 1.3±1.3 mg/L and controls 0.6±0.2 mg/L did not differ significantly. HDL cholesterol levels were 1.02±0.24 mmol/L for ACS visit 1, 1.00±0.3 mmol/L for ACS visit2, and 1.11±0.29 mmol/L for stable CAD. Plasma Lp-PLA2 levels were significantly higher in ACS visit1 subjects than in the ACS visit2 (144.3±60.6 vs. 89.5±40.0 ng/mL, p<0.0001). Interestingly, sCAD patients had slightly higher Lp-PLA2 levels that ACS visit 2 (p=0.003).
The distribution of Lp-PLA2 differed according to the technique used. We found that only approximately 45% of Lp-PLA2 mass remained in the lipoprotein fraction (d<1.21 g/L) after UTC, with the majority (43%) in the LDL fraction and only <3% in the HDL fraction. The remainder (55% was found in the d>1.21 g/L, suggesting that Lp-PLA2 is only loosely bound to lipoproteins, and the majority resides in LDL.
Here, we show that subjects with an ACS have markedly increased Lp-PLA2 levels acutely and that these levels fall within 12 weeks. Surprisingly, Lp-PLA2 is only loosely bound to lipoproteins and may be displaced in inflammatory conditions. The increase in Lp-PLA2 in ACS may contribute to the generation of oxidized fatty acyls and lysophopsphlipids and potentially compound the local inflammatory reaction.
Abstract 447: Treatment of Omega-3 Nutritional Deficiency Improves Cardiovascular Disease Risk Factors: Results of the Randomized, Double-Blind, Placebo-Controlled VASCAZEN-REVEAL Trial
Authors: Shaikh Nisar A , Ali Abbas , Yantha Jason , Shaikh Sabah , Jackowski George 
Published: March 2022

Introduction
Treatments with Omega-3 (OM3) formulations have been suggested to have cardio-protective effects. A strong association of high plasma OM3 levels has been correlated with reduced risk of sudden death and “risk quartiles” based upon OM3 levels, have been previously described. However, systematic studies describing the extent of OM3 deficiency, it’s correction by intervention, and improvement in CVD risk factors are lacking. Our study is the first to determine dietary levels of OM3 in plasma and in red blood cells using Omega-Score and Omega-3 Index diagnostics, improvement after treatment with a proprietary “>90%-pure OM3 preparation with a 6:1 EPA (eicosapentaenoic acid): DHA (docosapentaenoic acid) ratio” (6:1-OM3), and the concomitant beneficial effects on CVD risk factors in patients with high triglycerides (TG 200-500mg/dL).

Hypothesis
CVD patients are nutritionally deficient in OM3 fatty acids, and through treatment with 6:1-OM3, such deficiency can be corrected, improving CVD risk factors.

Methods
A double blind, placebo-controlled study comprised of 110 subjects randomized and stratified by baseline TG levels (A: 90-199 mg/dL, and B: 200-500mg/dL). This report includes placebo (corn oil, n=54) and 6:1-OM3 treatment (> 3g of EPA + DHA/day; n=56) groups at baseline and after 8 weeks of treatment. The primary endpoints were the change in the Omega-Score (OS) and Omega-3-Index (OI), with secondary endpoints including the change in serum TG, lipoprotein cholesterol (VLDL, LDL, HDL, ApoB, and subfractions), and hsCRP.

Results
89% of screened CVD subjects (N=655) were nutritionally deficient in Omega-3. In group B subjects, a significant (p<0.0001) increase in OS (121%) and OI (112%) was observed in treated subjects with a TG reduction of 48% (p=0.0005), VLDL-C reduction of 30% (p=0.0023) and HDL-C increase of 9% (p=0.0069) without significantly affecting LDL-C, ApoB or hsCRP levels.

Conclusions
This study confirms that omega-3 deficiency is prevalent with CVD, and that such a deficiency can be corrected with 6:1-OM3 resulting in a concomitant and significant placebo-corrected reduction in TG and VLDL, and increase in HDL-C in patients with high TG (200-500mg/dL), without adversely affecting LDL-C.
Abstract 450: Effects of Multiple Infusions of Recombinant LCAT on Plasma and Tissue Lipids and Expression of Genes Involved in Atherogenesis
Authors: Vaisman Boris , Rousset Xavier , Auerbach Bruce J , Krause Brian R , Homan Reyn , Freeman Lita , Ossoli Alice , Sampson Maureen L , Remaley Alan 
Published: March 2022

BACKGROUND
LCAT, an enzyme that converts small, discoidal HDL to spherical HDL particles by esterifying free cholesterol, plays a key role in reverse cholesterol transport (RCT). LCAT replacement therapy holds promise for treatment of familial LCAT deficiency, as well as a possible acute treatment in patients with Acute Coronary Syndrome.

HYPOTHESIS
Injecting recombinant LCAT into LCAT-deficient mice expressing human apoA-I will increase plasma HDL-C levels, improve reverse cholesterol transport, and alter expression of genes involved in atherosclerosis.

METHODS
We injected recombinant human LCAT or vehicle intravenously daily for 4 days into LCAT-KO x human apoA-I transgenic mice (n=4-6 in each group). The dose of rLCAT was approximately 10-fold larger in terms of mass than the endogenous levels of mouse LCAT. Lipids in plasma and tissues, as well as expression of 84 cholesterol metabolism genes in control and experimental groups were measured.

RESULTS

Total cholesterol (TC) in plasma increased from 80 (vehicle) to 473 mg/dl (LCAT) (
P
<0.002) after rLCAT treatment. Cholesteryl esters (CE) increased from 8 (vehicle) to 339 mg/dl (LCAT). Lipids were localized mostly in the HDL fraction. The accumulation of lipids in plasma was accompanied by decreased lipid content in peripheral tissues.TC in aorta, heart, kidney and spleen decreased, by 15%; 27%; 13% and 27%, respectively (
P
<0.05). In kidney, lung and spleen, CE decreased from 17; 18 and 28 nmol/mg dry weight, respectively, to being below detection. LCAT injections did not significantly alter liver lipid content, but did significantly increase expression of cholesterol synthesis genes (Dhcr7, Hmgcr, Mdv, Mvk and Tm7sf2) and decreased expression of the cholesterol efflux gene Abcg1.To further investigate the potential of interaction between apoA-I and LCAT, we also studied apoA-I-Tg x LCAT-Tg double transgenic mice. Their TC in plasma reached more than 1300 mg/mL, with similar gene expression changes observed in hapoA-I transgenic mice but more pronounced.

CONCLUSIONS
The results show the feasibility of using recombinant LCAT as a therapy for LCAT deficiency and for other diseases associated with accumulation of cholesterol in tissues.
Abstract 453: Is There a Relationship Between Platelet Count and Atherosclerosis Determined by Calcium Score in Patient With Acute Chest Pain?
Authors: Kassi Mahwash , Chaikriangkrai Kongkiat , Khan Zahoor , Khaleel bala Sayf , Cordero Andrea , Chang Su Min 
Published: March 2022

Background
Platelet interaction and the clotting cascade are known to play an important role in the process of atherosclerosisHowever, the relationship between platelet count and calcium scores is not well known.

Methods
This is a sub-group analysis of 974 consecutive patients who presented to our institution for chest pain without evidence of myocardial infarction. Calcium scores were determined in these patients using cardiac CT scans. The platelet count was divided in quartiles. Pearson’s correlation was used to test association between platelet count and calcium scores.

Results
The predominant gender was female (60%) and the mean age was 57. Sixty percent of the population was Caucasian. The mean Framingham score was 8.16 ± 8.15. There was no difference seen in the prevalence of low calcium scores (100) in different platelet groups when divided in quartiles. Similarly, there was no difference in mean calcium scores in different groups.

Conclusion
The serum platelet count does not correlate with calcium scores.
Abstract 467: Nitric Oxide-Mediated Regulation of the Adiponectin-Adiponectin Receptor Pathway Following Arterial Injury
Authors: Koo Nathaniel C , Havelka George E , Martinez Janet , Flynn Megan , Kibbe Melina R 
Published: March 2022

Objectives
Nitric oxide (NO) has been shown to limit the development of neointimal hyperplasia; however, little is known about its effects on the adventitia. Adiponectin is a molecule that originates from periadventitial adipose tissue and has been shown to negatively regulate neointimal growth. Thus, we hypothesize that removal of periadventitial fat from the arterial wall will negatively impact the ability of NO to inhibit the development of neointimal hyperplasia following injury.

Methods
The carotid artery injury model was performed on 11-week-old Sprague Dawley rats. Animal models underwent either removal of all periadventitial fat from the artery at the time of surgery (absent) or no disturbance of the periadventitial fat (present). Treatment groups included control, injury, and injury + NO (PROLI/NO, 10mg). Arteries were harvested at 2 weeks. Morphometric analysis was performed using ImageJ software. Immunofluorescent staining was performed for the adiponectin receptor (AR) and assessed using blinded grading (scale 0-4).

Results
Morphometric analysis revealed a 29% increase in neointima development in the absent vs. present group (p<0.001). With the application of NO, there was a greater decrease in intima area in the absent than the present group (93% vs. 77%, p<0.001). The results were similar for media area (50% vs. 37%, p<0.001) and the intima/media area ratio (86% vs. 65%, p<0.001). While AR staining showed no significant difference in the media or adventitia with the application of NO in the present group, AR staining was significantly increased in both the media (57%, p=0.009) and adventitia (37%, p<0.05) with the application of NO in the absent group.

Conclusions
Removal of the source of periadventitial adiponectin resulted in more neointimal hyperplasia following arterial injury, but a paradoxical NO-mediated increase in AR levels and corresponding responsiveness to NO therapy. These data suggest that AR expression is upregulated in the absence of adiponectin by NO. Further studies that identify the mechanism by which NO may regulate adiponectin may provide a novel therapeutic target to prevent neointimal hyperplasia.
Abstract 472: Fractional Flow Reserve (FFR): FAR FROM REALITY
Authors: Patel Chintan , Ahmed Sameer , Morsy Mohamed 
Published: March 2022

Fractional Flow Reserve (FFR) is the ratio of maximal blood flow in a stenotic artery to normal maximal flow. It is the “gold standard” technique used in diagnostic angiography to determine whether percutaneous intervention is needed in a moderate coronary stenosis (estimated 50-70% lesion). An FFR less than 0.8 may be falsely reassuring in a patient with unstable plaque who may be actively forming and dissolving clot.
This is a case of a 36 year old gentleman, with no significant past medical history, who presented to another local hospital with complaints of episodic chest pain that was located in the sub-sternal region and radiated to his left upper extremity. He was found to be mildly hypertensive, with elevated cardiac markers and with no EKG findings. On cardiac catheterization the patient was found to have a 50% lesion of left anterior descending artery and an FFR measurement of 0.93-0.91, therefore the lesion was not stented. The patient was subsequently discharged home. Two months later the patient presented to the hospital with crushing chest pain, and found to be having a ST elevation myocardial infarction. On repeat cardiac catheterization, the patient was found to have a 99% lesion of his left anterior descending coronary artery requiring placement of a drug eluting stent.
Cardiac catheterization is a life saving diagnostic and interventional modality for many patients with coronary artery disease. Fractional Flow Reserve is a new diagnostic tool used to guide management of coronary lesions with intermediate stenosis. It does not, however, take into account the pathophysiology of the lesion itself, for example a stable versus an unstable plaque. As in this case, a non flow-limiting lesion can still be unstable and plaque rupture can create a life-threatening myocardial event. With the development of intravascular ultrasound and optical computed tomography, the ‘gold standard’ seal of FFR will require reevaluation in regards to diagnostic modalities.
Abstract 473: Fluid Shear Stress Specifically Exacerbates Chlamydia pneumoniae-mediated Pro-inflammatory Responses in Monocytes
Authors: Evani Shankar J , Dallo Shatha F , Ramasubramanian Anand K 
Published: March 2022

Background and Significance
The precise role of Chlamydia pneumoniae infection in various stages of the atherosclerosis is not well understood. During the transit from lung to the atherosclerotic sites, C. pneumoniae-infected monocytes travel through circulation and are subjected to shear stress due to blood flow. Elucidating the effects of these mechanical stimuli on infected monocytes is critical in our understanding of the link between C. pneumoniae infection and atherosclerosis.

Objectives
We hypothesized that fluid shear stress alters the inflammatory response of C. pneumoniae-infected monocytes. Using an in vitro model of blood flow, we determined the effect of physiological levels of shear stress on monocyte responses pertinent to atherosclerosis including cytokine secretion, adhesion molecule expression, intracellular signaling, and endothelial adhesion.

Methods
Primary human monocytes and THP-1 cells were infected with C. pneumoniae at an MOI-2 for 2 h at 35 °C with intermittent rocking, and cultured for 36 h. The infected cells were then subjected to a shear stress of 7.5 dyn/cm2 for 1 h, and the supernatants were analyzed for a panel of 17 cytokines, and the cells were analyzed for signaling proteins, surface receptors, and endothelial adhesion. Uninfected cells and static conditions were used as controls, and a P<0.05 (Student’s t-test) was considered significant.

Results
We observed that shear stress on infected cells resulted in a caspase-independent upregulation of pro-inflammatory IL-1β (3-fold), a modest increase in MIP-1α and MIP-1β, a decrease in anti-inflammatory IL-10, and no change in other cytokines including TNFα and IL-12. These changes were manifested as an increase in the adhesion of monocytes to endothelium activated with the infected supernatants. We also observed differences in the chemotaxis of monocytes exposed to sheared vs. static supernatants.

Conclusions
We observe that physiological shear stress drives Chlamydia infected monocytes towards a pro-inflammatory state in circulation suggesting a critical synergy between mechanical and chemical factors in atherogenesis.