bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4759: Endothelin-1: A Useful Prognostic Marker After Acute Myocardial Infarction
Authors: Freixa Xavier , Doltra Ada , Ortiz José Tomás , Argiró Sergio , Guasch Eduard , Heras Magda , Jiménez Marcelo , Betriu Amadeo , Masotti Mónica 
Published: April 2024

INTRODUCTION: High Endothelin-1 (E-1) levels have been linked to poor clinical outcomes after myocardial infarction (MI). Vasoconstriction of the coronary microcirculation seems to be the underlying mechanism. However, the relationship between E-1 levels and microvascular integrity in the setting of MI has not been analyzed.
OBJECTIVES To assess the effect of E-1 on microvascular integrity, necrosis volume, left ventricular ejection fraction (LVEF) and myocardial savage (M-sav) in evolving MI.
METHODS: We measured E-1 levels in a consecutive series of 127 patients (pts) presenting with a first MI. Blood samples for E-1 measurements were taken 6 to 24 hours after MI onset. MRI was performed within 1 week following presentation and microvascular obstruction (MO), necrosis volume and LVEF was assessed by ce-CMR. M-sav was definded as the % of angiographic area at risk by the BARI score that spared necrosis on the MRI.

RESULTS: Mean age was 60.9±11,8 years and 94(80%) were males. MI location was anterior in 47.2%. As shown in table

, high E-1 levels were associated to admission Killip ≥2, higher prePCI TIMI 0, worse postPCI MBG and higher mortality at 30 days. MO was documented in 48%. High E-1 values were also associated with MO and worse M-sav while no significant correlation was obtained with necrosis volume and LVEF. Compared to Troponin I/CKMB peak values, E-1 levels showed better correlation with MO, M-sav, Killip on admission, MBG postPCI and mortality at 30 days.

CONCLUSIONS: In humans, high E-1 levels after MI are closely associated with the presence of MO and worse M-sav. E-1 assessment renders prognostic information, independent from that provided by LVEF and necrosis volume
Abstract 4760: Effect of Cyclosporine on Left Ventricle Remodeling After Reperfused Myocardial Infarction
Authors: Mewton Nathan , Croisille Pierre , Gahide Gerald , Rioufol Gilles , Bonnefoy Eric , Cung Thien Tri , Sportouch Catherine , Angoulvant Denis , Piot Christophe , Revel Didier , Ovize Michel 
Published: April 2024

Introduction: In a human study, administration of cyclosporine A at the time of acute myocardial infarction (AMI) reperfusion was associated with a smaller infarct size. However, experimental data suggest that cyclosporine A has a detrimental effect on left ventricular remodeling. This study examined the effect of cyclosporine A used at the time of reperfusion, on LV remodeling and function by cardiac magnetic resonance (CMR) in the early days and several months after AMI. Material and
Methods: 28 patients of the original cyclosporine A study had an acute (day 5) and a follow-up (6 months) CMR study. Cine imaging was used to determine LV volumes, mass, ejection fraction and myocardial wall thickness in infarcted and remote non-infarcted myocardium, and late gadolinium imaging was used to determine infarct size.
Results: There was a persistent reduction of the absolute infarct size at 6 months in the cyclosporine A group compared with the control group of patients (29±15 grams VS 38±14 grams; P=0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; P=0.07) in the cyclosporine A group, compared with the control group, both at day 5 and at 6 months after infarction. There was no significant difference between the two groups in either global LV mass or regional wall thickness of the remote non-infarcted myocardium at day 5 or at 6 months. Attenuation of LV dilatation and improvement of LV ejection fraction by cyclosporine A at 6 months were correlated with infarct size reduction.
Conclusion: Cyclosporine A used at the moment of AMI reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling.
Abstract 4841: The Impact of Chronic Uremia on Ichemic Preconditioning of the Myocardium
Authors: Mccafferty Kieran , Byrne Conor , Kieswich Julius , Yaqoob Magdi 
Published: April 2024

Background Ischemic Preconditioning (IPC) is a process by which brief non lethal periods of ischemia render the dependant tissue resistant to subsequent lethal injury. This process has been extensively studied in animal models and this has led to human clinical trials. There is evidence to suggest that additional co-morbidities may render hearts more resistant to the effects of IPC. There is no published data examining the effects of chronic uraemia on IPC. This is of clinical importance due to the burden of cardiovascular disease in CKD patients.
Hypothesises

Can uremic hearts respond to an IPC stimulus

Can uremic hearts respond to an IPC stimulus as well as non uremic hearts

Methods The 5/6 nephrectomy model (SNx) in male Wistar rats was used as a model of chronic uraemia. We performed 2 experiments to test the hypothesises. Expt 1: SNx rats were divided into 2 groups. The control group (n=15) underwent myocardial ischemia using reversible LAD artery ligation. The LAD was occluded for 25 minutes and reperfused for 2 hours. The IPC group (n=4) had 3 cycles of 5 minutes LAD ligation and 5 minutes reperfusion followed by 25 min occlusion and 120min reperfusion. Expt 2: SNX animals (n=8) and Sham controls (n=6) underwent x1 cycle of IPC as above with 35minutes ischemia 2 hours reperfusion. At the end of the experiment the animals were sacrificed and the infarct size was measured and expressed as a percentage of the area at risk (AAR).
Results Expt 1: Median Infarct size was 61.2% and 7.5% in the control and IPC groups respectively (P=0.003) Expt 2: Median infarct size was 16.8% and 43.7% in the SNX and sham SNx groups respectively. (P=0.008) The AAR was not significantly different in any of the groups studied.
Discussion This is the first evidence that unlike ‘old’ hypertensive rats and diabetic rats, uremic rats can respond to a preconditioning stimulus. Furthermore it appears that the preconditioning may confer greater protection in uremic animals than controls. We hypothesize that the significantly lower haemoglobin in the uremic animals reduces microvascular occlusion which may occur during IPC. Work is underway to quantify this finding.
Conclusion This study suggests that clinical trials using IPC in uremic patients could improve outcomes following cardiac interventions.
Abstract 4852: High Resting Velocity in Intramyocardial Coronary Artery is Related to Elevated Plasma Brain Natriuretic Peptide Levels in Patients With Hypertension
Authors: Doi Yasuji , Okada Ken-ichiro , Kaibe Shoji , Ito Noritoshi , Hayashi Tohru 
Published: April 2024

Narrowings in intramyocardial coronary arteries (IMCA) and elevated plasma brain natriuretic peptide (BNP) levels have been demonstrated in hypertensive heart disease. To clarify the relation between abnormalities in IMCA and plasma BNP levels, 228 consecutive patients with hypertension were studied using high-frequency transthoracic Doppler echocardiography. We defined IMCA flow as abnormal one if acceleration flow in IMCA, indicating the presence of vessel narrowing, was detected by color flow mapping and the pulsed Doppler study demonstrated higher peak diastolic flow velocity than 32cm/sec (i.e. normal value + 2SD) in the site. Such abnormal flow in IMCA was demonstrated in 59 (56%) of 102 hypertensive patients with left ventricular hypertrophy (LVH) and in 36 (24%) of the other 126 hypertensive patients without LVH. Independent of LVH, the 95 hypertensive patients with abnormal IMCA flow had higher peak diastolic velocities in the IMCA (47.9±16.5 cm/s vs. 24.3±5.4 cm/s, p<0.01) and more elevated plasma BNP levels (131.0±24.4 pg/ml vs. 45.8±5.7 pg/ml, p<0.01) than those without abnormal IMCA flow. Furthermore, peak diastolic velocities had a significant correlation with log BNP values (p<0.01). The index of % area stenosis (IAS) estimated by the continuity equation was 46±14% at the site of acceleration flow, indicating the presence of mild to moderate lumen narrowing in the IMCA. The patients with the IAS of 50% and over had significantly higher log BNP values as compared to those with the IAS of less than 50% (p<0.05), indicating plasma BNP levels may be elevated by factors associated with lumen narrowing in the IMCA.
Conclusions: High resting velocity in IMCA is at least partly related to elevated BNP levels in patients with hypertension independent of LVH.
Abstract 4858: Is Brachial Artery Diameter an Early Index of Organ Damage in Hypertension?
Authors: Schillaci Giuseppe , Pucci Giacomo , Mannarino Massimo R , Pirro Matteo , Pasqualini Leonella , Vaudo Gaetano , Mannarino Elmo 
Published: April 2024

Objectives: Arteries can enlarge in response to a variety of hemodynamic and non-hemodynamic stimuli. The role of vascular remodeling in atherosclerosis-free arteries in hypertension is poorly understood. We investigated whether brachial artery diameter (BAD), an index of vascular remodeling,

is increased in hypertensive patients, and

has a relationship with left ventricular (LV) mass, an important marker of target-organ damege in hypertension.

Methods: 463 never-treated subjects with uncomplicated essential hypertension (283 men, 180 women; age 48+/−11 years, office blood pressure 155/96+/−17/9 mmHg) underwent M-mode echocardiography, 24-h BP monitoring, and ultrasound assessment of end-diastolic non-dominant BAD. 96 healthy normotensive subjects (40% women) served as controls. Analyses were performed separately in men and women.
Results: BAD had significant direct associations with age, male sex, systolic blood pressure and body mass index. BAD was larger in hypertensive subjects than in normotensive controls (4.62+/−0.8 vs 4.48+/−0.7 mm, p=0.02). In hypertensive subjects, age-adjusted BAD values were higher in subjects with LV hypertrophy (LV mass >51 g/m2.7; 4.46+/−0.6 vs 4.04+/−0.6 mm in women, 5.13+/−0.7 vs 4.81+/−0.7 mm in women, both p<0.0001). In sex-specific multiple linear regression analyses (Table), BAD predicted LV mass index in both men (beta=0.17, p=0.003) and women (beta=0.13, p=0.043), independently from the effects of age, 24-hour BP and body mass index (all p<0.05).
Conclusion: Diameter of the brachial artery is increased in untreated hypertensive subjects. In hypertension, larger brachial artery diameter is associated with left ventricular hypertrophy, and this relation is partly independent from the effect of common predictive factors. Brachial artery diameter is a potential early marker of organ damage in hypertension.
Abstract 4871: Circulating Endothelial Microparticles: A Novel Biomarker for Prediction of Subsequent Death and Cardiovascular Events in End-stage Renal Disease
Authors: Amabile Nicolas , Boulanger Chantal M , Guérin Alain P , Tedgui Alain , London Gérard M 
Published: April 2024

Background: Endothelial dysfunction is closely associated with increased circulating levels of endothelial microparticles (EMPs) in patients with end-stage renal disease (ESRD). As arterial damage is a major contributor to cardiovascular mortality, we examined whether or not circulating levels of EMPs could predict outcome in ESRD.
Methods: This prospective study included 81 stable hemodialyzed patients with ESRD (age 59±14 yr; 63% male; follow-up 57 months). Baseline plasma microparticles (MPs) levels, cell origin and reproducibility were analyzed by flow cytometry. The primary end-point was the occurrence of any death. Secondary end-points included cardiovascular death and occurrence of major adverse cardiovascular events (MACE).

Results: Non-survivors (n=19) were older (70.6±9.2, vs. 55.1±13.2 y, p<0.001) and were characterized by lower diastolic blood pressure (70.8±10.5 vs. 80±12.4 mmHg, p<0.01), higher levels of hsCRP (6.9±4.4 vs. 5.0±4.3 mg/L, p<0.05) and endothelial CD31+CD41- EMPs (1822±1516 vs. 934±207 ev/
μ
l, p<0.001), whereas other MPs subtypes were not different. Mutivariate Cox analysis demonstrated that baseline EMPs levels independently predicted all-cause death (HR=4.0 [1.2–13.0] per log unit, p=0.02), cardiovascular mortality (HR=8.81 [2.4 –31.8], p<0.001) and MACE (HR=3.28 [1.2 – 8.9], p<0.01) after adjustment for age, traditional cardiovascular risk factors, medications and biological parameters. ROC curve analysis showed that baseline EMPs levels correctly predicted all-causes and cardiovascular mortality (AUC: 0.80±0.008 and 0.83±0.008 respectively, p<0.001 for all). EMP baseline level > 710 event/
μ
L correctly identified subsequent death with a sensitivity of 92% and a specificity of 63%. Kaplan-Meier analysis revealed that survival of patients with EMPs levels above median was worse than other patients (p<0.01, log rank analysis), whereas platelet MPs levels did not affect outcome.

Conclusions: Increased circulating levels of endothelial microparticles is a robust independent predictor of all-causes and mainly cardiovascular mortality in patients with ESRD and could help identify asymptomatic patients at higher risk of developing cardiovascular diseases and adjust therapy.
Abstract 4904: Comparative Anti-atherogenic Effects of a Single Intravenous Injection of rAAV8 Or rAAV2 Encoding Apo A-IMilano Gene
Authors: Tian Fung , Wang Lai , Yang Mingjie , Sharifi Behrooz G , Shah Prediman K 
Published: April 2024

Background: We previously reported potent anti-atherogenic effects of gene transfer of Apo A-IMilano through transplant of retrovirally transduced bone marrow. In anticipation of potential evaluation of Apo A-IMilano gene transfer in human atherosclerosis, we evaluated the comparative anti- atherogenic efficacy of Apo A-IMilano gene transfer using intravenous injection of type-2 and type-8 recombinant adeno-associated viruses (rAAV2 and rAAV8) as vectors in Apo A-I/apo E null mice.
Methods: Mice received one intravenous injection of 1.2×1012 vector genome copies of rAAV2 -Milano or rAAV2 -Control or rAAV8 -Milano or rAAV8 -Control (12 mice per group). Four weeks after injection mice were placed on high fat diet. Twenty weeks later mice were euthanized to analyze Apo A-IMilano gene expression and quantitative extent of aortic atherosclerosis after oil-red O staining. ELISA analysis of blood samples and real-time PCR analysis of target organs was used to determine the Apo A-IMilano gene expression. Blood was analyzed for cholesterol levels.
Results: The circulating cholesterol levels were comparably elevated among the 4 groups. Serum Apo A-IMilano levels were significantly higher in rAAV8 -Milano injected mice compared to rAAV2 -Milano injected mice at 4 weeks (71 ± 31 ng/ml vs. 31 ± 21ng/ml) 12 weeks (92 ± 61 ng/ml vs. 30 ± 27), and at 24 weeks (45 ± 32 ng/ml vs. 7.6 ± 6 ng/ml) (P <0.001 all groups). Real time PCR showed a significantly higher level of transgene expression in the heart (122 ± 36 fold), liver (32 ± 25 fold) and the brain (14 ± 0.39 fold) with rAAV8 -Milano compared to rAAV2 -Milano. Compared to rAAV8 -Control, the mean aortic lesion area was reduced by 42% by rAAV8 -Milano (7.7 ± 0.06% vs 13.4 ± 1.1 % of aorta; p = 0.001). Compared to rAAV2-Control, the mean aortic lesion area was reduced by 16% by rAAV2 -Milano (12.6 ± 0.8 vs 10.6 ± 0.8 % of aorta; p = NS). rAAV8 -Milano reduced lesion area by 27% compared to rAAV2 -Milano (p = 0.01).
Conclusions: Intravenous rAAV8 -Milano results in higher in-vivo transgene expression and a significantly greater reduction in aortic atherosclerosis compared to vector control or rAAV2 -Milano.
Abstract 4915: IQGAP1 Expressed in Macrophage and Endothelial Cells Plays an Important Role in ROS-dependent Ischemia-induced Neovascularization
Authors: Urao Norifumi , McKinney Ronald D , Fukai Tohru , Ushio-Fukai Masuko 
Published: April 2024

Not only endothelial cells (ECs) but also macrophage play a key role in ischemia-induced angiogenesis which is dependent on inflammation and reactive oxygen species (ROS). IQGAP1, an actin- and Rac1-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We demonstrated that IQGAP1 is involved in VEGF-induced ROS production and migration in cultured ECs; however, its role in post-ischemic neovascularization remains unknown. Using hindlimb ischemia model of mice, here we show that IQGAP1-expressing Mac3-positive macrophage and lectin-positive ECs (5.5 and 10.2-fold) are increased in ischemic limb tissues at 3 days and 7 days after ischemia, respectively. Ischemia-induced neovascularization is significantly impaired in IQGAP1 knockout (KO) mice as compared to wild-type (WT) mice as evaluated by laser Doppler blood flow (38% decrease), capillary density (48% decrease), and alpha-actin+ arterioles (68% decrease). In IQGAP1 KO mice, the number of infiltrated Mac3-positive macrophage and ROS production in ischemic muscles are significantly decreased (30% and 52%, respectively). In contrast, numbers of inflammatory cells and cKit+/Flk1+ endothelial progenitor cells (EPCs) in peripheral blood are not affected in these knockout mice. As compared to WT-BM transplantation to irradiated WT mice, WT-BM to irradiated KO mice inhibits ischemia-induced in blood flow recovery (22%) and CD31+ capillary density (5%), while KO-BM to irradiated WT mice shows decreases in flow recovery (48%) and capillary density (23%). These findings indicate that IQGAP1 KO mice impair function of BM derived cells without affecting their mobilization from BM. Furthermore, in vitro, BM-derived macrophages obtained from KO mice show defective polarization of actin (88% decrease), as visualized by phalloidin staining as well as inhibition of migration induced by SDF-1 (92%) or wound scratch (38%). VEGF- or wound scratch-induced EC migration is inhibited in IQGAP1-depleted ECs. In summary, IQGAP1 upregulated in macrophage and ECs after hindlimb ischemia plays an important role in ROS-dependent postnatal neovascularization. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent cardiovascular diseases.
This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract 4937: A Novel Molecular Imaging Sensor of Cellular Oxidative Stress
Authors: Peterson Karen M , Chen Ian Y , Simari Robert D , Gambhir Sanjiv S , Lerman Amir , Rodriguez-Porcel Martin 
Published: April 2024

Increased oxidative stress has been suggested to play an important role in the biology of mesenchymal stem cells (MSCs). However, little is known of the effect of increased oxidative stress in-vivo, partly due to the lack of appropriate imaging technologies for monitoring of stem cell biology in the living subject. Recent developments in molecular imaging permit, for the first time, the longitudinal monitoring of stem cell biology in vivo. We hypothesize that changes in oxidative stress can be monitored using a reporter gene strategy (molecular imaging).
Methods: We have developed a novel oxidative stress sensor, using a two-step transcriptional amplification strategy to enhance the expression of firefly luciferase (Fluc), driven by the pro-oxidant enzyme NAD(P)H promoter, and used to monitor oxidative stress in rMSCs. rMSCs was induced by hypoxia (1% O2 for 24 hours) and serum deprivation (SD) and confirmed using a dichlorofluorescein colorimetric assay (measures the production of hydrogen peroxide-H2O2-) and NAD(P)H protein expression.

Results: Both serum deprivation and hypoxia led to a pro-oxidant state (Fig. A–B

). Most importantly, increased oxidative stress led to increased activity of the novel reporter gene sensor (Fig. C

) which was decreased in the presence of antioxidants (superoxide dismuatse mimetic Tempol, 5mM, SD+T, Fig D

). Results were reproduced in a different cell type (rat cardiomyoblast, data not shown).

Conclusion: Changes in oxidative stress in MSCs can be monitored using molecular imaging. Reporter Gene-based Molecular Imaging, a strategy that is clinically applicable, provides the opportunity to monitor stem cell survival in the living subject.
Abstract 4965: High Mobility Group Box 1 Protein Expression is Associated With Expansion and Rupture of Human Abdominal Aortic Aneurysm
Authors: Kohno Takashi , Anzai Toshihisa , Kaneko Hidehiro , Shimizu Hideyuki , Shimoda Masayuki , Miyasho Taku , Okamoto Minoru , Yokota Hiroshi , Yamada Shingo , Yoshikawa Tsutomu , Okada Yasunori , Ishizaka Akitoshi , Yozu Ryohei , Ogawa Satoshi 
Published: April 2024

Background: Abdominal aortic aneurysm (AAA) expansion is characterized by widespread transmural inflammation and extracellular matrix degradation. High mobility group box1 protein (HMGB1) is one of the recently defined damage-associated molecular pattern molecules derived from necrotic and activated inflammatory cells, and functions as a proinflammatory mediator. The aim of this study was to elucidate the clinical significance of HMGB1 expression in patients with AAA.
Methods and Results: Serum HMGB1 concentration was measured by enzyme-linked immunosorbent assay in 40 patients with infrarenal AAA (6 patients with ruptured and 34 patients with nonruptured AAA), who underwent surgical repair of AAA. Serum HMGB1 level on admission did not differ between the presence or absence of atherosclerotic risk factors, including smoking, hypertension, hyperlipidemia, age and sex, and cardiovascular medications. These variables were similar between patients with ruptured and nonruptured AAA. Serum HMGB1 level was significantly higher in patients with ruptured AAA compared with nonruptured AAA (4.9±3.4 vs 1.9±2.9 ng/ml, p<0.05). Thirty-eight AAA tissues taken during surgical repair were examined for immunoblotting (4 ruptured and 34 nonruptured AAA). The HMGB1 level in aneurysmal tissue was positively correlated with AAA diameter (r=0.43, p<0.05). In addition, HMGB1 expression was higher in patients with ruptured AAA than those with nonruptured AAA (p<0.05). Gelatin zymography showed that matrix metalloproteinase (MMP)-2 and -9 levels were significantly elevated in the ruptured AAA compared with nonruptured AAA (all p<0.05). Patients with MMP-2 level>median value had a higher HMGB1 level in aneurysmal tissue than those without (p<0.05). Immunohistochemistry demonstrated that HMGB1 was highly expressed in macrophages and neutrophils within the degenerating aortic media and periadvential fat tissues of AAA. HMGB1 was also expressed in smooth muscle cells and fibroblasts within the degenerating aortic media.
Conclusions: Elevation of HMGB1 level in serum and aneurysmal tissue was observed in patients with expansion and rupture of AAA, in association with activation of MMPs. Serum HMGB1 could be a useful marker of the development of AAA rupture.