bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1392: Increased High Density Lipoprotein Cholesterol induced by Human Apolipoprotein A-I Gene Transfer increases Adiponectin Expression in abdominal Adipose Tissue
Authors: Van Linthout Sophie , Spillmann Frank , Foryst-Ludwig Anna , Bücker-Gärtner Carola , Meloni Marco , Feng Yingmei , Kintscher Ulrich , De Geest Bart , Schultheiss Heinz-Peter , Tschoepe Carsten 
Published: July 2021

Introduction: High density lipoprotein (HDL) cholesterol (C) levels positively correlate with plasma adiponectin levels. However, the role of HDL on adiponectin expression is unkown. To investigate the effect of increased HDL levels on adiponectin expression, 1) gene transfer with human apolipoprotein (apo) A-I, the main apo of HDL, was performed in control mice and in lipopolysaccharide (LPS)-injected mice, associated with decreased adiponectin levels and 2) HDL was supplemented in vitro on (pre)-adipocytes.
Methods: Eight weeks old male C57BL/6 mice were i.v. injected with 5 × 10e10 total particles of the E1E3E4-deleted adenoviral vector Ad.hapoA-I, expressing human apo A-I or with the same dose of Ad.Null, containing no expression cassette. Fourteen days hereafter, mice were i.p. injected with LPS from Escherichia coli at a dose of 80 mg/kg or with saline. Mice were sacrificed 12 hours after LPS or saline injection. Human apo A-I and mouse adiponectin plasma concentrations were determined by ELISA. Abdominal fat phospho (p) and total (tot.) Akt protein levels were determined by Western Blot; adiponectin mRNA expression of (pre)-adipocytes by real-time PCR.
Results: Ad.hapoA-I GT resulted in human apo A-I expression levels of 83Â27>4.6 mg/dl at day 14, which was associated with 1.8-fold (p<0.05) and 1.5-fold (p<0.05) higher HDL-C and adiponectin levels compared to Ad.Null mice, respectively. After LPS-injection, human apo A-I levels decreased by 1.7-fold (p<0.001), leading to 1.7-fold lower adiponectin levels compared to Ad.hapoA-I control mice, but still 1.5-fold (p<0.01) higher compared to LPS-Ad.Null mice. The increased adiponectin levels in Ad.hapoA-I versus Ad.Null LPS-injected mice were associated with a 1.7-fold (p<0.05) increase in p-Akt/tot.Akt ratio. In vitro, LPS administration decreased adiponectin expression by 2.1-fold (p<0.01), which was normalized to control levels by HDL supplementation in a phosphatidylinositol-3-kinase (PI3K)-dependent manner, since Ly 294002 reversed the HDL-mediated increase in adiponectin expression.
Conclusion: HDL increases adiponectin expression via the PI3K-Akt pathway, which may contribute to some of the pleiotropic actions of HDL such as its well-known anti-inflammatory effects.
Abstract 1444: Overexpression Of Endothelial Nitric Oxide Synthase Restores Post-natal Neovascularization In Atherosclerosis.
Authors: Mees Barend , Waeckel Ludovic , You Dong , Tempel Dennie , Godinho Maria , Van Haperen Rien , Lévy Bernard , de Crom Rini , Silvestre Jean-Sébastien 
Published: July 2021

Alteration in post-ischemic neovascularization is a common complication of atherosclerotic disease. This results, at least in part, from abrogation of bone-marrow mononuclear cells (BM-MNC) pro-angiogenic potential. Overexpression of eNOS has been shown to promote vessel growth in the setting of ischemia. We hypothesized that eNOS overexpression could restore impaired neovascularization in atherosclerotic (ApoE KO) mice. Hind limb ischemia was induced in mice by right femoral artery ligation. After two weeks we evaluated tissue perfusion of the foot by Laser Doppler, vessel density in the hind limb by micro-angiography and histology, and atherosclerotic plaque size. In vitro BM-MNC cell culture assays were performed. Tissue perfusion and vessel density were 1.5-fold increased in transgenic mice overexpressing eNOS (eNOStg) as compared to wild type (WT) (P<0.001, n=10). Transplantation of 1x106 WT- or eNOStg BM-MNC in WT recipients caused a 1.5-fold increase in tissue perfusion and vessel density compared to injection of PBS (P<0.001, n=10). Next, we used ApoE KO mice and crossbreeds of eNOStg and ApoE KO mice (eNOStg*ApoE KO). Tissue perfusion and vessel density were 1.8-fold increased in eNOStg*ApoE KO mice as compared to ApoE KO mice (P<0.001, n=10). Transplantation of both WT- or eNOStg*ApoE KO BM-MNC in ApoE KO recipients caused a 1.6- to 2-fold increase in tissue perfusion and vessel density compared to PBS (P<0.01, n=10), while transplantation of ApoE KO BM-MNC had no positive effect on neovascularization. Moreover, transplantation of WT BM-MNC significantly increased plaque size, while eNOStg*ApoE KO BM-MNC had no effect on plaque size. eNOS overexpression did not affect BM-MNC apoptosis and secretion of growth factors but increased their ability to differentiate in vitro into EPC.
Conclusion: eNOS overexpression in the endothelium improves post-ischemic neovascularization in both physiological as atherosclerotic settings. Furthermore, eNOS overexpression in the bone marrow restores the impaired pro-angiogenic potential of atherosclerotic BM-MNC without adverse effects on plaque size. Therefore, overexpression of eNOS could play a vital part in the development of therapeutic angiogenesis for atherosclerotic disease.
Abstract 1517: Does Angiogram Make A Difference In The Outcome Of Acute Coronary Syndrome? A Study On Sex Difference In Outcomes In South America.
Authors: Bugiardini Raffaele , Rolandi Florencia , Bazzino Oscar , Manfrini Olivia , Pascua Andres , Botto Fernando , Fuselli Juan , Matas Carlos Rojas , Estrada Jose L Navarro 
Published: July 2021

HYPOTHESIS. Women presenting with acute coronary syndrome are less likely to have significant coronary artery disease (CAD) than men, which could narrow wide differences in sex outcomes when evaluating the study population as a whole.
METHODS. The Prognosis in Acute Coronary Syndromes Registry enrolled 823 patients (591 men and 232 women) who had been hospitalized for an acute coronary syndrome without ST-segment elevation and had undergone cardiac catheterization. We explored sex-based differences in presentation and outcomes, sorted by angiographic groups: obstructive (≥50% stenosis, accordingly to quantitative computerized analysis) versus non-obstructive CAD. Patients were followed up for 6 months.
RESULTS. In obstructive CAD, women were older than men (71.4 ± 9.7 versus 64.4 ± 11.1 years, p<0.001), and had significantly higher rates of hypertension (51.9% versus 39.7%, p<0.001). Women were less likely to have smoked (19.3% versus 29.8%, p<0.01). A smaller percentage of women than men had non-ST elevation myocardial infarction as an index event (7.7% versus 22.8%, p<0.001) and positive troponin value (51.3% versus 67.4%, p<0.01). At follow-up women showed no differences in myocardial infarction, rehospitalization for unstable angina or revascularization, but they did suffer an increased rate of cardiovascular death (8.4% versus 3.4%, p<0.01), with a hazard ratio 2.34 (95%CI: 1.13– 4.84, p=0.023). Relation between sex and death remained significant even after adjustment for any confounders (hazard ratio 2.48; 95%CI: 1.19–5.15, p=0.015). In non-obstructive CAD group, the clinical characteristics and prognostic end-points (death: 0% men versus 1% women) did not significantly differ between men and women.
CONCLUSIONS. In conclusion, women with obstructive CAD suffer an increased rate of cardiovascular death after acute coronary syndrome. Inclusion of large numbers of women with non-obstructive coronary disease in calculations based on the entire cohort may mistakenly shift results toward apparent outcome similarity with men.
Abstract 1553: Comparative Gene Expression Analysis of Blood and Heart Identifies Genomic Predictors of Myocardial Injury Following Cardiopulmonary Bypass and Cardioplegic Arrest in the Rat
Authors: Podgoreanu Mihai V , Yoshitani Kenji , Dobra Adrian , Ma Qing , Zhu Bin , Mackensen G B 
Published: July 2021

Background: Perioperative myocardial injury (PMI) complicating cardiac surgery remains poorly predicted by clinical risk factors. In a novel rat model of cardiopulmonary bypass (CPB) and cardioplegic arrest (CA) we tested the hypothesis that microarray expression profiles in peripheral blood leukocytes (PBL) can accurately predict degree of PMI, and compared genomic signatures in left ventricular myocardium (LVM) and PBL to identify PMI-associated genes that generalize across tissues.
Methods: Male rats subjected to CPB only (75 min), CPB with CA (30 min), and sham surgery (n=5 each) had plasma heart fatty acid binding protein (HFABP) and cardiac troponin I (cTnI) measured 1 hour post CPB and microarray profiling of total RNA from LVM and PBL. PMI genomic classification models were constructed using shotgun stochastic search approach and Bayesian model averaging and their accuracy tested by five-fold cross validation.

Results: A spectrum of PMI was observed in the experimental groups as well as robust deregulation of gene expression in a stimulus and tissue-specific manner (Figure

). Estimates of PMI classification accuracy from PBL and LVM are presented in Table

.

Conclusions: Cardiac surgery induces changes in leukocyte gene expression that predict the spectrum of PMI, with potential applications in perioperative risk stratification and selection of cardioprotective strategies.

Predictive accuracy of tissue-specific myocardial injury genomic classifiers
Abstract 1566: Tumor Necrosis Factor Receptor 2 Signaling Protects Myocardial Function Following Ischemia In Females Via Stat3, Socs3 And Vegf
Authors: Wang Meijing , Crisostomo Paul , Markel Troy , Meldrum Daniel R 
Published: July 2021

Introduction: Myocardial ischemia/reperfusion (I/R) increases local TNF production, which contributes to myocardial dysfunction; however, the mechanisms remain incompletely understood. Some investigations have shown that TNF may be protective and others have shown it to be injurious. Our previous studies have shown that females have improved myocardial functional recovery, TNFR1 signaling resistance, and increased SOCS3 expression following acute I/R when compared to males. However, the effect of TNFR2 on gender differences in myocardial functional recovery following I/R is unknown. We hypothesized that

TNFR2 mediates myocardial protection from I/R through STAT3, SOCS3 and VEGF in both genders,

TNFR2 elicits greater protective signaling in females as compared to males.

Methods: Isolated male and female mouse hearts (Langendorff) from TNFR2 knockout (TNFR2 KO), TNFR1/2KO and wild type (WT) (n=3– 6/group) were subjected to 20 minutes of ischemia followed by 60 minutes of reperfusion. Myocardial function (+/−dP/dt) was continuously monitored. After I/R, hearts were analyzed for STAT3, SOCS3 and VEGFa gene expression (RT real-time PCR), STAT3 activation (Western blot). Two-way ANOVA or student’s t-test, p<0.05 statistically significant.
Results: TNFR2 deficiency decreased post-ischemic recovery of +/−dP/dt in both genders, but with greater effect on females. This deleterious effect of TNFR2KO was associated with a decrease in gene expression of VEGFa to 38%, STAT3 to 51% and SOCS3 to 36% in female TNFR2KO hearts, but without significant change in males. Additionally, TNFR1/2 KO decreased myocardial function in female hearts, but not in males. Interestingly, TNFR1/2 deficiency increased gene expression of VEGFa by 37%, SOCS3 by 30% in males, but decreased VEGFa by 48%, STAT3 by 45% and SOCS3 by 49% in females. Moreover, STAT3 activation was decreased in female TNFR2KO and TNFR1/2KO hearts.
Conclusions: TNFR2 mediates myocardial protection through VEGF, STAT3 and SOCS3 following I/R in both genders, but with a relatively greater benefit of TNFR2 signaling observed in females. These data expand upon gender-based TNF signaling in myocardium, which may in part explain certain clinical differences with important therapeutic implications.
Abstract 1681: Evaluation of Quantitative Myocardial Perfusion MRI and TIMI myocardial blush grade (Blush score)
Authors: Nakajima Hiroshi , Okamoto Shinya , Sakuma Hajime , Kurita Tairo , Nagata Motonori , Fujimoto Naoki , Masaki Ishida , Takeda Kan , Ito Masaaki 
Published: July 2021

Background: The TIMI myocardial blush grade (MBG) has been shown to be a strong angiographic predictor of mortality in patients with TIMI 3 flow after primary angioplasty. This study was conducted to evaluate the relationship between regional myocardial perfusion quantified by cardiac magnetic resonance and angiographic reperfusion score defined by MBG.
Methods: We studied 29 consecutive patients (25 men, age 63±13 years) with ST-segment elevation acute myocardial infarction (LAD lesion: 12, RCA lesion: 16, LCx lesion: 2) who underwent primary angioplasty within 6 hours from the onset and showed TIMI grade 3. MBG was determined on angiography at the end of angioplasty. All patients underwent rest myocardial perfusion MRI during initial hospitalization, and regional MBF (ml/min/g) was quantified by using a Patlak plot method. Myocardial perfusion (MP) ratio was calculated from quantitative perfusion MRI, as MBF in infarction area/MBF in normal area. The optimal cut-off value of MP ratio that can predict MBG 3 on coronary angiography was determined by using a receiver-operating characteristic (ROC) analysis.
Results: In 29 patients with TIMI 3 flow after angioplasty, 4 patients had MBG 0–1, 7 had MBG 2 and 18 had MBG 3. The MP ratio in MBG 3 group calculated from quantitative perfusion MRI was significantly higher than the MP ratios in MBG 0 –1 group and MBG 2 group (0.96±0.18 vs. 0.48±0.25, P<0.001; 0.96±0.18 vs. 0.66±0.19, P=0.003, respectively). There was no significant difference between the MP ratios in MBG 0 –1 group and MBG 2 group. The ROC curve revealed that MP ratio of 0.74 is an optimal threshold to distinguish MBG 3 from MBG 0 –2, with a high area under the curve of 0.90.
Conclusions: The result of this study demonstrates that MP ratio quantified from rest perfusion MRI correlated well with MBG on coronary angiography.
Abstract 1701: Soluble Receptor for Advanced Glycation End Products (RAGE) is a Prognostic Factor for Heart Failure
Authors: Koyama Yo , Takeishi Yasuchika , Niizeki Takeshi , Suzuki Satoshi , Kitahara Tatsuro , Sasaki Toshiki , Kubota Isao 
Published: July 2021

Background: It is known that oxidative stress is increased in patients with heart failure. Advanced glycation end products (AGE) are generated nonenzymatically by glycation and oxidation of proteins. We have recently reported that serum level AGE is an independent prognostic factor for heart failure. Receptor for AGE (RAGE) has a secretory isoform of the receptor protein, termed soluble RAGE. In the present study, we measured serum soluble RAGE levels in patients with heart failure.
Methods: Serum soluble RAGE level was measured in 160 patients with heart failure and 40 control subjects. Patients were prospectively followed with endpoints of cardiac death or re-hospitalization.

Results: Serum soluble RAGE level was increased with advancing NYHA functional class (figure 1

). We determined the cut-off value of serum soluble RAGE level to predict cardiac events from ROC curve analysis as 1220 pg/ml (sensitivity 0.60, specificity 0.69). As shown in figure 2

, high serum soluble RAGE groups (>1220 pg/ml) had a significantly lower cardiac event-free rate (P = 0.0004) than low serum soluble RAGE groups (≥ 1220 pg/ml). In the univariate Cox proportional hazard analysis, serum soluble RAGE, age, NYHA functional class, creatinine, B-type natriuretic peptide (BNP), left ventricular end-diastolic diameter (LVEDD) were significantly associated with cardiac events. In the multivariate Cox proportional hazard analysis, serum soluble RAGE and plasma BNP were independent risk factors for cardiac events (soluble RAGE: HR 2.22, 95% CI 1.08 - 4.53, P = 0.029; BNP: HR 2.86, 95% CI 1.11 - 7.37, P = 0.029).

Conclusions: Serum soluble RAGE level is a novel independent prognostic factor for heart failure.
Abstract 1738: Lone Atrial Fibrillation: Long-Term Clinical and Echocardiographic Follow-up from the Canadian Registry of Atrial Fibrillation
Authors: Leong-Sit Peter , Humphries Karin H , Lee May , Klein George J , Sheldon Robert , Connolly Stuart J , Green Martin S , Talajic Mario , Dorian Paul , Kerr Charles R 
Published: July 2021

Background: The natural history of lone atrial fibrillation (AF) is unclear with conflicting data in the literature. We aimed to better describe the clinical outcomes and echocardiographic changes associated with lone AF.
Methods: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled 803 non-surgical and non-flutter patients with new onset AF between 1990 and 1996. At enrollment, patients were classified as lone AF (LAF) or not lone AF (Not LAF) based on structural heart disease or hyperthyroidism. Clinical data was prospectively collected with follow-up at 3 months, 1 year, then annually; echocardiograms were performed at enrollment and years 2, 4, and 7.

Results: The LAF group (n=212) had a median age of 57 (1
st
quartile 44, 3
rd
quartile 67) while the Not LAF group (n=591) had a median age of 67 (59, 73), p<0.0001. During the median follow-up of 8 years in the LAF group and 7 years in the Not LAF group, there was a significant difference in survival free from stroke or embolism favoring the LAF group (Figure

). At 8 years, the probability of remaining free of chronic AF was 78.8% vs 69.3% (p=0.02) and free of symptomatic or documented recurrence of AF was 40.1% vs 26.9% (p<0.01) in the LAF vs Not LAF group. The LAF group had smaller LV diastolic and systolic dimensions by 5.5% and 10.2%, respectively, vs the Not LAF group (p<0.0001). The LV mass was smaller at baseline by 21.1% (p<0.0001) vs the Not LAF group, but increased at a greater rate (4.0% vs 0.9%/2 years, p<0.0001).

Conclusions: Lone AF, compared to non-lone AF, is associated with a lower rate of death, stroke or embolism, recurrence and progression to chronic AF. Interestingly, LV mass increased significantly only in the Lone AF group.
Abstract 285: Granzymes: Major Players in Vascular Remodelling, Atherosclerosis and Longevity
Authors: Cruz Rani P , Boivin Wendy A , Chamberlain Ciara M , Choy Jonathan C , McManus Bruce M , Granville David J 
Published: July 2021

Introduction: Granzymes A and B (GrA/GrB) are cytotoxic proteases that are released by immune cells to eliminate target cells. GrB is present in human vessels and its expression corresponds to increased disease severity. In addition to their cytotoxic roles, in conditions of chronic inflammation, GrA and GrB may contribute to the degradation of extracellular matrix (ECM) proteins leading to tissue degeneration.
Hypothesis: GrA and GrB levels are elevated in atherosclerotic patients and play a key role in the degradation of ECM and atherosclerosis.
Methods: ApoE −/− x GrB −/− double knockout (apoE/GrB-DKO) mice were generated. C57-wt, GrB-KO, apoE-KO or apoE/GrB-DKO mice were fed a high fat diet for 30 weeks, sacrificed, tissues processed and lesion morphology and morphometry assessed. GrA and GrB levels were also measured in human plasma from patients with or without clinically evident atherosclerosis by ELISA. GrA/GrB-mediated ECM proteolytic activity was also assessed.
Results: GrB deficiency significantly reduced the development of xanthomatosis, hair loss and atherosclerosis in the apoE-KO mice. GrB deficiency resulted in a marked reduction of elastin degradation in both the skin and blood vessels. GrB was found to co-localize to elastin fibres in atherosclerotic plaques and was capable of binding to, and cleaving elastin in vitro. ECM cleavage assays demonstrated that GrA and GrB cleave other ECM such as fibronectin. Preliminary studies indicate that GrB deficiency increases the lifespan of the apoE-KO mice as the apoE/GrB-DKO mice can survive up to 60 weeks of age on a high fat diet with no external indication of disease, skin degeneration or hair loss. In humans, preliminary evidence indicates that GrA/GrB levels are elevated in atherosclerosis. Smoking also appears to elevate plasma granzyme levels.
Conclusions: During chronic inflammation, granzymes accumulate extracellularly and exhibit proteolytic activity towards extracellular matrix proteins that results in vascular remodeling and atherosclerosis with age. Attenuation of GrB resulted not only in a significant reduction of atherosclerosis, but also prolonged the lifespan of apoE-KO mice.
Abstract 1812: More CPR with the New Guidelines. Does it Impact VF Termination by Defibrillation Shocks?
Authors: Hersan Olivier , Jost Daniel , Banville Isabelle L , Calamai Franck , Fontaine David , Lallement David , Chapman Fred W , Walker Rob G , Degrange Herve , Fuilla Claude 
Published: July 2021

The 2005 resuscitation Guidelines emphasize reducing interruptions of cardiopulmonary resuscitation (CPR) and provide changes to the CPR and defibrillation protocols for automated external defibrillator (AED) use. We investigated whether the differences between Guidelines 2000 and 2005 resuscitation protocols influence the ventricular fibrillation (VF) termination rate of AED shocks during out-of-hospital cardiac arrest.
Methods: As part of a clinical trial, VF cardiac arrest patients treated by firefighters were prospectively randomized to treatment protocols consistent with Guidelines 2000 (CONTROL) or Guidelines 2005 (STUDY). The STUDY protocol removed stacked shocks and post-shock pulse checks. It featured 1 minute of CPR before the 1st shock, and CPR between rhythm analysis and shock delivery. All AEDs delivered escalating biphasic shocks beginning at 200J. We reviewed AED electronic records to evaluate VF termination for all shocks within the first 8 minutes of treatment. Successful defibrillation was defined per Guidelines 2005 as termination of VF for > 5seconds. A sample size of 400 shocks per group was prospectively chosen for statistical power to detect an 8% difference in VF termination rate.
Results: As expected, the STUDY protocol resulted in more prompted CPR time, more actual CPR delivered, and fewer shocks during the first 8 minutes of treatment. The VF termination rate did not differ between the two groups (85% CONTROL vs. 87% STUDY). The proportions of patients with ventricular complexes (24% vs. 27%), in asystole (61% vs. 60%), or remaining in a shockable rhythm (15% vs. 13%) at 5 seconds were also not different between the CONTROL and STUDY groups, respectively.
Conclusion: Despite a reduction in CPR hands-off time, VF termination effectiveness of biphasic shocks is similar for Guidelines 2000 and Guidelines 2005 cardiac arrest treatment protocols.