bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 604: Influence of Perivascular Adipose Tissue on Vasodilation in Metabolic Syndrome
Authors: Kagota Satomi , Maruyama Kana , Iwata Saki , Wakuda Hirokazu , Yoshikawa Noriko , Nakamura Kazuki , Shinozuka Kazumasa 
Published: March 2022

Metabolic syndrome facilitates the development of cardiovascular disease due to atherosclerosis. We propose that chronic oxidative-nitrative stress is linked to the development of vascular dysfunction in response to nitric oxide (NO) in the coronary and mesenteric arteries of SHRSP.Z-
Lepr
fa
/IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome. Perivascular adipose tissue (PVAT), which is located outside blood vessels, has now been recognized as playing a role in vascular function. We assessed the role of PVAT in vascular dysfunction observed in SHRSP.ZF rats with metabolic syndrome.

We used SHRSP.ZF rats at 13, 18, and 23 weeks, and observed obesity, hyperlipidemia, glucose intolerance, and hypertension from 13 weeks until 23 weeks of age. Relaxation induced by acetylcholine and sodium nitroprusside were unchanged in isolated mesenteric arteries of SHRSP.ZF rats at 13 weeks of age, but were impaired at 18 and 23 weeks of age compared to those in control Wistar-Kyoto rats (WKY). The relaxation induced by both agonists was greater in the mesenteric arteries enveloped by PVAT than in those without PVAT in SHRSP.ZF rats at 18 and 23 weeks of age. The relaxation in the arteries with PVAT in SHRSP.ZF rats were at similar levels as those in the arteries without PVAT in age-matched WKY. In contrast, no difference was observed in the relaxation levels in the arteries with and without PVAT in SHRSP.ZF rats at 13 weeks of age and in WKY at all ages. Histological analysis of PVAT showed that adipocytes in PVAT of SHRSP.ZF rats at 20 weeks of age were larger than those observed in WKY. Impaired NO-dependent vasodilation was also observed in aortas of SHRSP.ZF rats at 23 weeks of age compared to that in age-matched WKY, but the relaxation was not altered by the presence of PVAT.
SHRSP.ZF rats with metabolic syndrome showed impairment in the NO-dependent pathway in resistant arteries, with increasing age/exposure to metabolic abnormalities. PVAT may help in the regulation of vasodilation to compensate for the impaired vasodilation observed under pathophysiological conditions, such as metabolic syndrome.
Abstract 363: Aortic Walls From Cadavers With Atherosclerosis Show Autoimmune Reactions: Exudation of Proteoglycans, Globulins And Interleukin-17, and Infiltration of Plasma Cells.
Authors: Nagareda Tomofumi , Hirata Nobuaki , Ohsawa Masahiko , Tanaka Sayaka , Kosakai Yoshio , Kimata Koji , Hatano Sonoko 
Published: March 2022

Athersclerosis is known to be caused by inflammation of aortic intima. In order to elucidate the mechanism of atherosclerosis, we investigated the inflammated changes of media of the ascending aorta associated with coronary artery disease in 44 biopsy specimens. The findings made us confident that inflammation occurs not only in the intima but also in the media of the atherosclerotic aorta, and also made us suspect that atherosclerosis may be caused by an autoimmune reaction. Here, we investigate proteoglycans, globulins, lymphoid cells, and interleukin-17 (IL-17) infiltrating into the wall of atherosclerotic aorta from cadavers, to confirm this idea.
Twenty cadavers from 32 to 93 years old were studied. We divided the subjects into 4 groups with 5 cases each: 1-20% as a slight group, 20-50% as a mild group, 50-75% as a moderate group, and 75% or more as a severe group, in terms of the percentage of atheromatous lesion from the ascending to the abdominal aorta. We immunohistochemically stained the ascending aortic wall with antibodies: LY111 for chondroitin-4-sulfate, 2B1 for Versican core protein, LCA and CD4 for lymphocytes, IL17 for cells positive for this, CD68 for macrophage, and CD38 for plasma cells. In addition, using the aortic wall, we delegated the protein electrophoresis demarcation and the measure of the values of IL-17 to a laboratory corporation.
Chondroitin-4-sulfate was stained diffusely positive in the entire wall. Versican showed characteristic patchy figure in the media. The numbers of patchy figures were significantly more in the mild and moderate groups than those in the slight and severe groups. In a similar manner, the numbers of plasma cells in the intima and media were significantly more in mild and moderate groups than those in the slight and severe groups. Protein electrophoresis showed the state of chronic inflammation. Among the 4 groups, the values (pg/mg) of IL-17 of mild (307.572±91.341) and moderate (183.027±30.926) groups were significantly increased compared with those of slight (108.310±43.008) and severe (69.812±17.465) groups.
The changes of the infiltration of plasma cell, the exudation of proteoglycans and also the increase of IL-17 in the wall make it more confident that atherosclerosis is related to an autoimmune reaction.
Abstract 661: Tie2 Deficiency Leads to Lymphatic Defects and Resistance to High-fat Diet Induced Obesity
Authors: Yamaguchi Shinji , Thomson Benjamin R , Heinen Stefan , Economides Aris N , Quaggin Susan E 
Published: March 2022

The Angiopoietin-Tie2 signaling pathway is a critical regulator in vascular development, with conventional Ang1 or Tie2 knockout mice dying in utero with vascular defects. While the role of this pathway in vascular development is apparent, the severity of developmental phenotypes makes it difficult to study Tie2 in vivo. Here, we investigate the functional role of Tie2 in embryonic as well as adult mice using inducible knockout mouse models (Tie2 cKO).
Tie2 inactivation at early stages of gestation (E12.5 or E14.5), which coincides with the initial stages of lymphatic development and remodeling, resulted in severe subcutaneous edema in E16.5 and altered lymphatic vessel morphology in the dermis of E17.5. These results indicate the important role of Tie2 in lymphatic development. In contrast, Tie2 inactivation at later stages (E18.5-P0) resulted in the birth of viable pups, indicating that Tie2 is dispensable after embryonic development. Adult male Tie2 cKO mice have similar blood glucose, glucose tolerance, and plasma lipids compared to controls. However, body weight of Tie2 cKO mice upon high-fat diet feeding was lower than that of control mice (47.5+-0.6g (control) vs. 38.0+-2.0g (Tie2 cKO), p<0.01 (4weeks after high-fat diet feeding)). Although plasma lipids (cholesterol and triglyceride) in control and Tie2 cKO mice were similar after high-fat diet feeding, mRNA expression of TNFa (100+-14% (control) vs. 40+-1.4% (Tie2 cKO), p<0.05) and F4/80 (100+-13% (control) vs. 53+-7.3% (Tie2 cKO), p<0.05) in epididymal fat were reduced in Tie2 cKO mice.
Our data show that Tie2 plays an import role in lymphatic development during embryogenesis and that Tie2 signaling is also important for adipose tissue growth in adult mice.
Abstract 711: In Hospital Complications After PCI After Insertion of DES versus BMS in the United States
Authors: Khoshchehreh Mahdi 
Published: March 2022

Background:
We evaluated the potential differences in patient complications and in-hospital mortality for patients who underwent primary percutaneous coronary intervention (PCI) with insertion of drug-eluting coronary artery stent (DES) versus those with insertion of bare metal stent (BMS) in the United States.

Method:
We used the Nationwide Inpatient Sample to examine differences in all-cause in-hospital mortality between DES versus BMS patients with a principal diagnosis of STEMI, NSTEMI and Coronary atherosclerosis ICD-9 codes. Bivariate and adjusted logistic regression analysis were used to identify any associations with DES versus BMS with increased subsequent complications and in-hospital mortality.

Results:
We identified 9140 admissions with PCI as a primary intervention, of which 85.03% native coronary artery stenosis, 5.9% presented with NSTEMI, 4.9% had STEMI, and 4.0% revascularized due to graft stenosis. Patients with graft stenosis and STEMI had the highest rates of BMS insertion (62% and 49% respectively).

The odds of in-hospital mortality were higher for BMS insertion among all for different group. However, the association lost the statistical significance after adjusting for patient characteristics, except for patients with native coronary artery stenosis (OR =1.96 95% CI: 1.02-3.8).
Major complications, including vascular, neurological, and mechanical complications were higher for BMS insertion for NSTEMI and graft coronary atherosclerosis patients. However, BMS insertion associated with less complication in STEMI patients and native coronary atherosclerosis. the later didn’t reach the statistical significance level. Interestingly, there was no in-hospital mortality in our sample among male with DES insertion.

Conclusion:
The clinical context of PCI and choice of DES versus BMS, with BMS a preferential choice in patients with evidence of thrombus (STEMI) is reflected in downstream complications and in-hospital mortality.
Abstract 15941: The Effects of Training and Detraining on T Wave Inversion in Athletes
Authors: Malhotra Aneil , Varkey Sneha , Dhutia Harshil , Walker Mike , Narain Rajay , Merghani Ahmed , Millar Lynne , Papadakis Michael , Sharma Sanjay 
Published: March 2022

Introduction:
T wave inversion (TWI) is the electrical hallmark of primary cardiomyopathies which are substrates for sudden death in young athletes. Such repolarization anomalies can feature on the ECG of an apparently healthy athlete and pose major diagnostic dilemmas in sports cardiology. Athletes are reluctant to detrain during the season.

Hypothesis:
This study hypothesized that detraining would affect TWI in athletes.

Methods:
Between 2013-2014, 36 professional footballers demonstrated TWI at mid-season ECG screenings (trained period). They were followed up during the "off-season" after a period of detraining (6-8 weeks). TWI was defined as –0.1 mV or greater 2 or more contiguous leads: anterior leads-V2-V3/4; inferior-II,III,aVF; or lateral-beyond V4 +/-aVL.

Comparisons were drawn by 2 independent cardiologists, between trained and detrained ECGs. All players were also investigated for an underlying cardiomyopathy.

Results:
*Athletes were male, aged 24.5+/-2.7 years.

*27 (75%) were Afro-Caribbean and 25% Caucasian (p=0.0141).
*TWI was most common in the anterior leads (n=20, 55%), followed by inferior (n=10, 28%) and lateral (n=6, 17%) as in the bar chart.
*No Caucasian player had TWI laterally.
*After detraining, 16 players demonstrated resolution of anterior TWI (80%, p=0.0293), 8 in inferior leads (80%, p=0.2353) and 4 in the lateral leads (67%, p=0.638) (Figures 1a & b).
*All players with abnormal TWI according to consensus guidelines were evaluated with no cardiomyopathy identified.

Conclusions:
In athletes who detrained during the 'off-season', we observed resolution of TWI in the majority of athletes (both Afro-Caribbean and Caucasian) after a relatively brief period of detraining which may be a physiological phenomenon. This was statistically significant in the anterior leads.

However, TWI in the inferior and/or lateral leads should always raise the suspicion of an underlying cardiomyopathy, especially if persistent after detraining.
Abstract 17001: Reconstituted High-density Lipoprotein (CSL-111) Infusion Improves Post-ischemic Heart Function Through Modulating the Acute Inflammatory Response and Angiogenesis
Authors: Richart Adele , Heywood Sarah , Reddy-luthmoodoo Medini , Natoli Alaina K , Kiriazis Helen , Du Xiao-Jun , Siebel Andrew , Kingwell Bronwyn 
Published: March 2022

Aims:
High-density lipoprotein (HDL) has multiple actions which may benefit post-ischemic heart function. We have shown in patients with type 2 diabetes that a single infusion of reconstituted HDL (rHDL, CSL-111) reduces inflammation1 including the number of circulating monocytes, neutrophils and lymphocytes. Whether such effects may contribute to improved heart function after ischemia and reperfusion is unknown. This study aimed to determine the effect of HDL on post-ischemic inflammatory response and heart function in insulin resistant mice.

Methods and Results:
A left coronary artery ligation model was used to study acute ischemia (30min) and reperfusion (I/R) in mice fed a chow (CD) or high fat diet (HFD) for 8 weeks. A single intravenous bolus of rHDL (CSL-111; 80mg/kg) or placebo (saline) was delivered at the time of reperfusion.

At 15 days post I/R, rHDL increased ejection fraction from 40±3% to 48±2% in both diet groups (p=0.004). rHDL also increased stroke volume (p=0.002) and cardiac output in both diet groups (p=0.015). Histological analysis revealed that rHDL increased the myocardial capillary density by 22±4% and 15±4% in CD and HFD mice respectively (p=0.0007; p=0.042). However, rHDL did not alter cardiomyocyte hypertrophy.
Interestingly, rHDL infusion modulated acute post-ischemic inflammatory response by decreasing the total number of circulating leucocytes (p=0.030) and neutrophils (p=0.005) in both diet groups 1 day following I/R. However, rHDL reduced the number of circulating monocytes (p=0.044) and B lymphocytes (p=0.009) only in HFD mice. In both diet groups, at 3 days post-I/R, rHDL reduced recruitment of leukocytes into the heart including monocytes (p=0.038, p=0.014), neutrophils (p=0.005, P=0.020), T lymphocytes (p=0.044, p=0.018) and B lymphocytes (p=0.043, p=0.010). Moreover, rHDL decreased the proportion of B lymphocytes recruited into the heart in HFD mice only (p=0.040), highlighting its strong anti-inflammatory effect particularly in the insulin-resistant state.

Conclusion:
A single infusion of rHDL at time of reperfusion improves post-ischemic heart function through modulation of angiogenesis and acute inflammatory response in insulin-resistant mice.
Abstract 17353: B Cell Depletion Promotes Aortic Infiltration of Tolerogenic Immune Cells and is Protective of Experimental Aortic Aneurysm
Authors: Schaheen Basil , Downs Emily A , Su Gang , Zhao Yunge , Srikakulapu Prasad , McNamara Coleen A , Butts Cherié , Upchurch Jr. Gilbert R , Meher Akshaya K , Ailawadi Gorav 
Published: March 2022

Anti-CD20 antibody-mediated B cell depletion therapy is widely used for the treatment of B cell malignancies and rheumatoid arthritis. Given the observation that B cells are abundant in abdominal aortic aneurysms (AA), we hypothesize that B cell depletion would be protective of experimental AA formation.
C57BL/6j and IL-10 knock-out (KO) mice (male, 8-10 weeks old) were injected intraperitoneal (IP) or intravenous (IV) with mouse monoclonal anti-CD20 IgG2a (or IgG2a control) antibodies at day 7 before and day 7 following induction of AA using the elastase AA perfusion model. AA size was measured at day 14 following perfusion. Depletion of B cell (B1, B2 and IL-10 producing B cells) was confirmed using flow cytometry or immunohistochemistry. IgG and IgM levels were quantified using ELISA. One-way ANOVA was used for data analysis.
B1 cells were prominent in peritoneal cavity, whereas B2 cells were spleen and blood. 85-95% of B1 and B2 cells were depleted at day 7 following both IP and IV treatments. Interestingly, both the treatments strikingly suppressed AA growth (control, 96±8%; IP, 62±5%; and IV, 55±4%, p<0.01, n=8-10). Plasma IgM levels were significantly lower (p<0.01), whereas, IgG levels were similar in the B cell depleted mice compared to control mice. Immunohistology showed IL-10 producing B cells were preserved in spleen of B cell depleted mice. B cell depletion in IL-10 KO mice partially suppressed AA formation (control, 111±6%; anti-CD20, 92±8%; n=4-5) suggesting AA growth was partly dependent on IL-10 producing B cells. Flow cytometry revealed presence of CD19+ with B220+ or CD20+, CD138+ (plasma cells), CD1d+ and IgM+IgD+ cells in AA of control mice, which were absent in B cell depleted mice. Despite the preservation of elastin layers, B220+ cells were found the in the AA of B cell depleted mice, which were CD20- and IDO+ (Indole 2,3-dioxygenase), suggesting they are T cell tolerogenic plasmacytoid dendritic cells (pDC). Correlated with this, the CD4+FoxP3+ regulatory T cell population was higher in the aorta of B cell depleted mice.
The present results suggest B cell depletion protects mice from experimental AA formation partly via preserving IL-10 producing B cells and promoting the presence of tolerogenic pDCs in the aorta.
Abstract 17586: HSP27 Mediated Atheroprotection Requires GM-CSF Induction: Potential Role in Reverse Cholesterol Transport?
(Best of Basic Science Abstract)
Authors: Pulakazhi Venu Vivek Krishna , Adijiang Ayinuer , Shi Chunhua , Chen Yong-Xiang , O’Brien Edward R 
Published: March 2022

Introduction:
Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces experimental atherogenesis and patients with elevated serum HSP27 levels are relatively protected against future CV events. We previously reported that extracellular HSP27 activates the NF-kB pathway and increases the expression of GM-CSF. While the potential atheroprotective role of GM-CSF remains controversial, clinical reports highlight its effect on reducing serum cholesterol levels. We now hypothesize that GM-CSF plays an important role in HSP27-mediated atheroprotection, potentially by up-regulating reverse cholesterol transport (RCT).

Methods / Results:
1. NF-KB signaling in vitro: Treatment of macrophages with recombinant HSP27 (rHSP27) activated NF-kB 15-fold via TLR-4 (NF-kB reporter gene assay; controls: truncated rHSP27 peptide and TLR-4 deficient cells; p<0.05). While rHSP27 substantially induced GM-CSF expression and secretion (300- and 400-fold respectively; p<0.05) both processes were blocked by NF-kB inhibitors.

2. In vivo role of GM-CSF induction in HSP27-mediated atheroprotection: Aortic atherogenesis in apoE null treated with rHSP27 was reduced by an expected 40%, while ApoE null / GM-CSF null did not respond to rHSP27 treatment. Moreover, apoE null / GM-CSF null macrophages expressed ~33% lower levels of the reverse cholesterol transporters, ABC-A1 and ABC-G1.
3. rHSP27 & Reverse Cholesterol Transport: THP-1 macrophages pre-treated with oxLDL and incubated with rHSP27 for 24h showed enhanced mRNA and protein expression of ABCA1 and ABCG1 (p<0.01). In a RCT assay, THP-1 macrophages labeled with NBD-cholesterol and treated with rHSP27 for 24h before being incubated with apoA1 or HDL showed increased cholesterol efflux compared to controls (p<0.0001 for both).

Conclusion:
HSP27 up regulates expression of GM-CSF that appears to play an important role in RCT-mediated atheroprotection.
Abstract 21021: Functional Regulatory Mechanism of Smooth Muscle Cell-Restricted
LMOD1
Coronary Artery Disease Locus
Authors: Nanda Vivek , Wang Ting , Iyer Dharini , Pjanic Milos , Liu Boxiang , Nguyen Trieu , Miano Joseph M , Quertermous Thomas , Leeper Nicholas J , Miller Clint L 
Published: March 2022

Coronary artery disease (CAD) remains the leading cause of mortality and morbidity worldwide and has an estimated heritability of 40%. Meta-analyses of genome-wide association studies have now identified 73 genome-wide significant loci and the most recent multi-ethnic meta-analysis identified a number of arterial wall-specific loci. One of these loci include the smooth muscle cell-restricted factor, LMOD1 (Leiomodin 1), a member of the actin filament nucleator family that is highly enriched in smooth muscle tissues including main arteries and visceral organs of the gastrointestinal system. We hypothesized that LMOD1 may serve as a potent marker of the phenotypic modulation of smooth muscle cells during atherosclerosis.
We recently identified a non-coding regulatory variant, rs34091558, which is in linkage disequilibrium with the lead CAD GWAS variant, rs2820315 (P=7.7E-10; OR=1.05). However, the causal mechanism for how these variants alter LMOD1 expression/function and CAD risk remains unclear.
Expression quantitative trait loci (eQTL) mapping in GTEx and STARNET databases confirmed that rs34091558 is among the top eQTLs for LMOD1 in vascular tissues. Allelic expression imbalance analyses in heterozygous HCASMC donors further demonstrated cis-acting effects on LMOD1 gene expression. Position weight matrix (PWM) motif analyses identified the protective allele at rs34091558 to form a consensus forkhead box O3 (FOXO3) binding motif, which is predicted to be disrupted by the risk allele. FOXO3 chromatin immunoprecipitation and reporter assays demonstrated reduced FOXO3 binding and transcriptional activity by the risk allele in HCASMC. Platelet-derived growth factor BB (PDGF-BB) stimulation also significantly reduced LMOD1 expression coincident with FOXO3 knockdown. Finally, both gain and loss-of-function for FOXO3 and LMOD1 in HCASMC delineated a regulatory circuit by which LMOD1 decreased HCASMC proliferation and migration and increased cell contraction.
Taken together, these results provide compelling functional evidence that: 1) common genetic variation is associated with dysregulation of LMOD1 expression, and 2) changes in vessel wall processes through LMOD1 dysregulation may partially explain the heritable risk for CAD.
Abstract 11316: Analytical Validation for an Integrated Risk Tool for Cardiovascular Disease Combining Conventional Risk Factors and Polygenic Risk Inferred from Snp Array and Low-Pass Whole Genome Sequencing
Authors: Giner Delgado Carla , Gradovich Eva , Sivley R. Michael , Rehnstrom Karola , Heger Andreas , Tarran William , Lachapelle Alexander , Donnelly Peter , Weale Michael E , McVean Gilean , Seth Priyanka , Plagnol Vincent 
Published: March 2022

Genetic risk factors contribute to cardiovascular disease (CVD) risk and are imperfectly captured by family history. The development of integrated risk tools (IRT) that integrate polygenic risk scores (PRS) with conventional risk factors enables improved risk assessment. However, IRTs rely on accurate estimation of the genetic component across millions of genetic variants, either typed or imputed.
To support two real-world implementations of CVD IRTs, we present analytical validation data for three biosample types (whole blood, saliva and buccal swab samples) and two genetic assay technologies (a custom-designed genotyping array (845,608 markers) and low pass whole genome sequencing (lpWGS) with 1.8x average read depth, both combined with computational imputation) across 48 ethnically-diverse donors. IRT measurements (range 4%-23%) were performed on the 10-year CVD risk percentage scale, assuming a non-genetic (pooled cohort equations) risk component of 10%.
We find measurement errors are below 1% across the three biosample types, so that an IRT of 4% will at most be measured as 3% or 5%. Array and lpWGS showed different bias-variance trade offs. The array technology was more reproducible, with a standard deviation on the percentage scale of 0.09 (0.072-0.129 95% CI) for blood samples compared with 0.30 (0.201-0.617 95% CI) for lpWGS. In contrast, the array technology showed somewhat larger bias when compared with high depth sequencing data (mean absolute error on the percentage scale of 0.49 (0.217-0.755 95% CI) for blood samples against 0.30 (0.008-0.597 95% CI) for lpWGS, partially reflecting the sequencing basis of the reference data. Pass rate was high for both technologies and all three biosample types.
In conclusion, both genotyping array and lpWGS approaches were appropriate and performed well for the purpose of assessing the genetic component of integrated cardiovascular disease risk using either blood, saliva or buccal samples.