bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4905: High Density Lipoprotein is Dysfunctional in Primary Antiphospholipid Syndrome and is Associated With Impaired Vascular Function
Authors: Charakida Marietta , Besler Christian , Batuca Joanna , Sangle Shirish , Alves José , D’Cruz David , Tousoulis Dimitris , Mackworth-Young Charles , Lüscher Thomas , Deanfield John 
Published: April 2024

Objectives: Antiphospholipid syndrome is characterised by increased thrombogenicity and/or pregnancy morbidity in the presence of raised levels of antiphospholipid antibodies (aPL). Increased oxidative properties of HDL (decreased activity of paraoxonase (PON) and accelerated atherosclerosis have been described in this syndrome. In this study, we assessed the functional properties of HDL and evaluated its impact on the vasculature in aPL positive patients and matched controls.
Methods: We studied 77 women with positive aPL (APL) aged 46.6 ± 1.2 yrs (mean ± SE) and matched Controls of 77 women aged 47.5 ± 1.2 yrs. In all subjects, carotid intima media thickness (IMT), flow mediated dilatation (FMD) and pulse wave velocity (PWV) were measured. PON activity was assessed by measuring p-nitrophenol formation. HDL was isolated in APL (N = 6) and Controls (N = 6). The impact of HDL on human aortic endothelial cell (HAEC) nitric oxide (NO) and superoxide production were determined. Anti-inflammatory properties of HDL were examined by analyzing the effect of HDL on endothelial cell VCAM-1 expression and monocyte adhesion to activated HAEC.
Results: APL had significantly increased IMT and PWV compared to Controls (0.75 ± 0.02mm vs 0.65 ± 0.01mm, p < 0.001 and 9.14 ± 0.18 m/s vs 8.56 ± 0.21m/s, p < 0.05 respectively) and decreased FMD (6.2 ± 0.5% vs 9.6 ± 0.5%, p < 0.001). PON activity was significantly reduced in APL compared to Controls (p = 0.006). PON activity was inversely associated with cIMT and PWV in APL (p < 0.05 for both) but not in Controls. HDL from Controls increased endothelial cell NO production, whereas in marked contrast HDL from APL reduced NO production by 20% (p < 0.0001). The beneficial effect of HDL on endothelial VCAM-1 expression, superoxide production and monocyte adhesion was diminished in APL (p < 0.05 for all).
Conclusions: APL is associated with impaired vascular function and structure. PON activity is decreased in APL and is inversely associated with IMT and PWV. HDL in APL is associated with decreased endothelial NO production and has impaired anti-inflammatory and anti-oxidant properties.
These findings suggest that HDL is dysfunctional in APL and support its role in promoting early vascular changes in antiphospholipid syndrome.
Abstract 4928: Coronary Flow Reserve is Reduced in Pulmonary Arterial Hypertension Patients
Authors: Yamada Osamu , Tsuda Etsuko , Ohuchi Hideo 
Published: April 2024

Background: Pump function of the right ventricle, which is a major determinant of prognosis in pulmonary arterial hypertension (PAH), is much influenced by coronary perfusion. Acute studies in animals exhibited paradoxical coronary flow decrease under excessive pressure overload. However, little is known about human or chronic coronary flow reserve (CFR) in PAH.
Methods: Coronary flow measurement with pulse Doppler was performed for 19 PAH consecutive patients (right ventricular systolic pressure RVSP 89.7±22.7 mmHg; age 22.0±5.5 year; 10 females, data are mean±SD). The control state blood velocity was recorded in distal right coronary artery (RCA). The maximal blood velocity was recorded at the same site, on continuous infusion of adenosine triphosphate (150ng/kg/min). CFR was defined as the ratio of peak adenosine/baseline flow velocity. RVSP was adopted from the most adjacent catheterization. Coronary arterial lesions were excluded with coronary angiogram.
Results: RCA flow signals were achieved in 17/19. Systolic flow signals were observed in 2/17. RCA diastolic peak velocity in basal condition was somewhat higher than reported in normal subjects (29.9±11.4 cm/sec) and positively correlated with right ventricular systolic pressure (RVSP) with significance (R^2 = .236; p<0.05). CFR of RCA ranged 1.55– 4.16 (2.46±0.82) and was below 2.0 in 7/17. It negatively correlated with RVSP (R^2 = .383; P < 0.01).
Conclusion: Peak flow velocity of RCA in PAH correlated with RVSP, in reply to greater energy demand of RV. CFR of RCA was low and negatively correlated with RVSP, which may suggest poor energy supply reserve in PAH patients.
Abstract 5153: Platelet Activation and Inflammatory Response in Patients With Non-dipper Hypertension
Authors: Kaya Mehmet , Yarlioglues Mikail , Gunebakmaz Ozgur , Gunturk Ertugrul , Inanc Tugrul , Dogan Ali , Kalay Nihat , Topsakal Ramazan 
Published: April 2024

Objective: We aimed to determine whether MPV and hs-CRP levels are elevated in non-dipper patients compared to dippers and healthy controls. In addition, we tried to find out if MPV and CRP are related to each other or not in non-dipper hypertensives.
Method: The total 126 patients study group included 86 patients with hypertension and 40 healthy subjects (16 male, mean age; 51±4) as control. Ambulatory blood pressure monitoring was performed for all patients. Hypertensive patients were divided into two groups; 46 dipper patients (18 male, mean age; 50±9) and 40 non-dipper patients (17 male, mean age; 53±11). Clinical baseline characteristics were similar between groups. We measured mean platelet volume in a blood sample collected in EDTA tubes and high-sensitive CRP was measured by using BN2 model nefelometer.
Results: Non-dipper patients demonstrated higher levels of MPV compared to dippers and normotensives (9.72±0.52 vs 9.38±0.33 and 8.92±0.42, p<0.05, respectively). High-sensitive CRP levels were also significantly higher in non-dippers compared to dippers and normotensives (4.9±1.7 vs 3.8±1.5 and 2.7±0.8, p<0.05, respectively). There was significant positive correlation between MPV and CRP levels (p=0.002, r=0.482) in non-dipper hypertensives.
Conclusion: Our results suggest that patients with non-dipping tend to have increased platelet activation and inflammatory response. Increased platelet activation and inflammatory response could contribute to increase the atherosclerotic risk in non-dipper patients compared to dippers.
Abstract 5160: Apelin Modulates Adipocyte and Inflammatory Cell Processes to Inhibit Atherosclerosis
Authors: Kojima Yoko , Kundu Ramendra , Leeper Nicholas J , Chun Hyung J , Quertermous Thomas 
Published: April 2024

Background: The G-protein coupled receptor APJ and its ligand apelin have many physiological roles in the cardiovascular system, although its overall impact and mechanism of effect on atherosclerosis remain controversial.
Methods and Results: Apelin knockout male mice were bred with ApoE knockout (ApoE KO) mice to generate double knockout (DKO) mice. DKO and ApoE KO mice were fed a normal diet for 20 weeks, and atherosclerotic lesions were analyzed histologically in the aortic sinus and by en face analysis. DKO mice developed more atherosclerosis in the thoracoabdominal aorta than ApoE-KO mice (percent plaque area; 5.36±0.55 vs. 2.53±0.54, p<0.05). Lesion area in the aortic sinus was also increased in DKO compared to ApoE-KO (0.30±0.14 vs. 0.15±0.04 mm2, p<0.05). Histological analysis showed that there was no difference in macrophage or smooth muscle content between genotypes, and studies of reactive oxygen species also did not show a significant difference. Because of recent evidence that the apelin-APJ pathway modulates insulin action, we investigated metabolic parameters and those associated with insulin resistance in the mouse models. DKO mice had significantly greater body weight and fat weight, and glucose tolerance testing showed the DKO mice to be insulin resistant. Also, the mRNA expression of TNF-a, IL-6, and MCP-1 in visceral fat tissue was increased in DKO compared with ApoE KO mice. Similarly, in cultured NIH 3T3 cells, apelin treatment decreased LPS-induced MCP-1 mRNA expression. In related studies, we investigated macrophage function in a foam cell assay, and found there was increased CD36 mRNA in aorta, and increased oil red O positive staining cells in peritoneal macrophage preparations from DKO mice compared with those from ApoE-KO mice.
Conclusion: Apelin-APJ signaling inhibits atherosclerosis through multiple mechanisms, including modulation of inflammation and metabolic effects in macrophages and adipose tissues.
Abstract 5493: Genetic or Acquired CYP2C19 Enzyme Deficit is Associated With an Excess of Cardiovascular Risk in Clopidogrel-treated Patients
Authors: Hulot Jean-sebastien , Collet Jean-Philippe , Silvain Johanne , Pena Ana , Bellemain-Appaix Anne , Barthélémy Olivier , Anzaha Ghalia , Beygui Farzin , Montalescot Gilles 
Published: April 2024

Introduction: Metabolic activation by CYP2C19 has emerged as a crucial determinant of clopidogrel responsiveness and efficacy. An increased risk of cardio-vascular events has been associated with the CYP2C19*2 allele, which causes loss-of-function, and with the use of proton pump inhibitors (PPI), which may also inhibit the CYP2C19, in clopidogrel-treated patients. We performed a meta-analysis to further estimate the relative effect in both sub-groups.
Methods: Sixteen published or presented studies evaluating the association between the loss-of-function CYP2C19*2 genetic variant (8 studies, 9427 patients) or the use of PPI (8 studies, 35108 patients) and outcomes in patients treated with clopidogrel were included. Data on the occurrence of ischemic events (death, recurrent myocardial infarction, urgent revascularization) were extracted and combined using a fixed-effect model.
Results: Of the 9427 patients, carriers of the loss-of-function CYP2C19*2 allele (28%, n=2674) displayed a 30% increase in the risk in any ischemic events compared to non carriers (10.4% vs 8.3%) (OR, 1.31; 95% CI, 1.12–1.53; p<0.001). This single gene variant (CYP2C19*2) was also associated with an excess of cardiovascular mortality (1.8% vs 1.0%)(OR 1.79; 95% CI: 1.10–2.91, p<0.019)(n=6225). PPI users (43%, n=15197) displayed an increased risk of ischemic events compared to non users (25.5% vs 19.4%) (OR, 1.48; 95% CI, 1.40–1.57; p<0.001)(n=34496). This metanalysis also showed an excess of mortality (16.9% vs 11.5%)(OR 1.20; 95% CI: 1.08–1.33, p<0.001)(n=15157) in PPI users compared to non users. When combining all data, CYP2C19 alteration due to the deficient allele or drug interaction has a 50% increased risk of ischemic events occurrence in clopidogrel treated patients (OR 1.49; 95% CI: 1.42–1.57, p<0.001).
Conclusions: CYP2C19*2 carriers and/or PPI users are patients exposed to a significantly increased risk of cardiovascular events when they are treated with clopidogrel.
Abstract 5518: Abnormal Coronary Flow Reserve is Related to Impairment of Left Ventricular Function During Adenosine Stress Echocardiography in Untreated Hypertensive Patients
Authors: Ikonomidis Ignatios , Tzortzis Stavros , Lekakis John , Triantafyllidi Helen , Papadopoulos Costas , Tsitlakidis Costas , Paraskevaidis Ioannis , Kremastinos Dimitrios T 
Published: April 2024

Objective: Coronary microcirculation is disturbed in hypertensive patients. We investigated the effects of coronary flow reserve (CFR) on the response of Left Ventricular (LV) systolic and diastolic function as assessed by Tissue Doppler Imaging during adenosine stress echocardiography in never-treated hypertensive patients.
Methods: We studied 43 patients (mean age: 53±12 years), with untreated arterial hypertension (clinic blood pressure >140/90 mmHg and >125/80 mmHg in 24hour ambulatory BP monitoring) by adenosine stress echocardiography and 22 healthy controls matched for sex, age and atherosclerotic factors. We measured:

time integral (VTI-Vd) of diastolic (Vd) coronary blood flow velocity by transthoracic Doppler echocardiography of the LAD

Ratio of VTI-Vd after adenosine infusion (140
μ
g/kg/min) to VTI-Vd at baseline to assess CFR

E and A doppler, Sm, Em, Am lateral mitral annulus velocities with TDI, Em/Am ratio and E/Em ratio before and during adenosine infusion to assess LV systolic and diastolic function,

the percent % changes of the measured indices between baseline and peak adenosine infusion.

Results: All patients had normal baseline ejection fraction. Compared to controls, hypertensives had lower CFR (2.3±0.7 vs. 2.9±0.9, p=0.03). At baseline, hypertensives compared to controls, had lower Em/Am ratio (0.9±0.3 vs. 1.3±0.4, p=0.002), Sm (8.7±1.7 vs. 9.7±2.6, p=0.07), Em (10.1±2.8 vs 12.1±3.5, p=0.03) and higher Am (11.1±2.5 vs. 9.5±2.0, p=0.03). At peak adenosine infusion there were an increase in Sm, Em and Am in all patients (p<0.05). Furthermore a decreasing CFR was associated with a decreasing Em (r= 0.46, p=0.05), Em/Am (r=0.49, p=0.048) and increasing E/Em (r=−0.4, p=0.04). A reduced CFR was related with a smaller % increase of Sm (r= −0.40, p=0.049), % increase of Em (r=− 0.5, p=0.033) and higher % increase of E/Em (r=−.42, p=0.04) at peak stress. Patients with CFR<2.5 (n=28), compared to those with CFR≥2.5 had lower % change of Sm (27±20% vs. 51±34% p=0.04), % change of Em (8±3% vs. 46 ±3%, p=0.05) and higher % increase of E/Em (24±3% vs −1±2%, p=0.04).
Conclusions: An abnormal response of LV function during adenosine stress echocardiography is related with impaired CFR in untreated hypertensive patients.
Abstract 5540: Clarithromycin Attenuates Periodontal Bacteria-Induced Abdominal Aortic Aneurysms With Altered Expression of Matrix Metalloproteinases
Authors: Aoyama Norio , Suzuki Jun-Ichi , Ogawa Masahito , Izumi Yuichi , Hirata Yasunobu , Isobe Mitsuaki 
Published: April 2024

Background: Matrix metalloproteinase (MMP) activity is known to be up-regulated in the abdominal aortic aneurysm (AAA). Periodontopathic bacteria were detected at a high rate of specimens of aortic walls from AAA patients. A major macrolide antibiotic, clarithromycin (CAM) has many biological functions including MMP regulation. However, little is known about the effect of CAM in AAA via MMPs. Thus, our purpose was to clarify the role of MMPs regulated by CAM in the progression of periodontopathic bacteria-induced AAA.
Methods and results: AAA was produced by periaortic application of 0.25M CaCl2 and subcutaneous infection of Porphyromonas gingivalis (Pg). We administered CAM (100mg/kg) to mice with AAA once a day for 28 days after CaCl2 application. After the infection with Pg, the plasma level of anti-Pg immunoglobulin-G was increased 2.1-fold (once infected) to 4.0-fold (repeatedly-infected) than the native. Four weeks after application of CaCl2, vehicle-treated mice showed the significant increase in aortic diameter (71±5%). However, CAM treatment significantly suppressed AAA development (12±1%). The CAM-treated mice showed the suppressed plasma level of MMP-9 (71±44 ng/ml) compared to control mice (91±22 ng/ml) using enzyme-linked immunosorbent assay (ELISA). As a compensatory action, the CAM-treated mice also exhibited less plasma level of tissue inhibitor of metalloproteinase (TIMP)-1 (1.96 ng/ml) than control (2.29 ng/ml) by ELISA.
Conclusion: These findings demonstrated that CAM prevented Pg-induced AAA development through the suppression of macrophage derived MMP production. Therefore, CAM could be clinically applicable for prevention of AAA development.
Abstract 5566: Serum Tenascin-C Levels Might be a Novel Biomarker for Predicting Short-term Prognosis of Type B Acute Aortic Dissection
Authors: Nozato Toshihiro , Sato Akira , Hirose Shunsuke , Koura Kenji , Yagishita Atsuhiko , Takahashi Yoshihide , Kamiishi Tetsuo , Hikita Hiroyuki , Takahashi Atsushi , Isobe Mitsuaki , Hiroe Michiaki 
Published: April 2024

Backgrounds: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is not normally expressed in adult heart and aorta, but transiently reappears under various pathologic conditions playing important roles in tissue remodeling. The aim of this study is to clarify the clinical implication of serum TN-C levels in patients with type B acute aortic dissection (AD).
Methods: We evaluated 43 patients with type B acute AD between May 2005 and January 2008 and 20 normal controls. We measured serum TN-C levels by ELISA on admission, 7 days, 14 days and 28 days after admission. We compared serum TN-C levels with blood biomarkers, and short-term clinical outcome at a discharge.
Results: Serum TN-C levels (66.4 ng/ml) in AD was significantly higher than normal controls (27.4 ng/ml) at admission (p<0.01). Serum TN-C levels in AD significantly increased at 7 days (82.4 ng/ml), and then gradually decreased to normal range at 28 days (40.4 ng/ml). Serum TN-C levels at 7 days was positively correlated with peak C-reactive protein levels (R=0.45, p=0.02). Three patients of AD died. Serum TN-C levels at 7 days of the death group were significantly higher than those of survival group (79.8±51.5 vs. 168.6±98.6 ng/ml, p=0.01).
Conclusions: We demonstrated that serum TN-C levels are significantly elevated during acute stage after AD, and might be a novel biomarker for prediction of patient prognosis with type B acute AD.
Abstract 5643 The Erythropoietin Heterodimeric Beta Common Receptor is in a Complex With and Requires VEGFR2 for Downstream Signaling
Authors: Segal Mark , Diao YanPeng , Sautina Laura 
Published: April 2024

Background: Endothelial progenitor cells (EPC) circulate in the bloodstream and are capable of carrying out endothelial repair. Erythropoietin (EPO) has been shown to have stimulatory effects on EPC. We have previously demonstrated that EPO effects EPC mobility and increases nitric oxide (NO) levels within cells via the heterodimeric beta-common receptor (BCR) and EPO receptor (EPOR). We now test the hypothesis that not only does EPO induction of NO by the BCR/EPOR complex require vascular endothelial growth factor receptor 2(VEGFR2), but VEGFR2 signaling itself requires the BCR.
Methods: EPC colonies isolated from human or mice were incubated with various kinase or VEGF inhibitors for 30 minutes prior to treating 50 mU/mL EPO and determining the bioavailable nitric oxide (NO) by DAF-FM-Diacetate. In addition we examined the ability of EPO and VEGF to promote an increase in NO in EPC isolated from the BCR −/− mice.
Results: The EPO induced increase in NO could be completely blocked with a VEGFR2 blocking antibody but not by an antibody against VEGF itself. Blocking VEGFR2 also inhibited the EPO mediated increase in transcription of the RNA for endothelial and inducible NO synthase. Interestingly, the increase in NO was not blocked by a JAK-2 kinase inhbitor (Tyrphostin AG-490) confirming that the EPO induced NO effects are independent of the homodimeric EPO receptor-JAK kinase pathway. Most importantly EPC isolated from the BCR−/− mice had no NO stimulation in response to EPO, or VEGF but had a normal NO stimulation in response to bradykinin. We also demonstrate that the VEGFR2 co-immunoprecipitates and colocalizes with the BCR.
Conclusion: We conclude that many of the tissue-protective effects of EPO demonstrated in models of ischemic, traumatic, and inflammatory injuries may be occurring through horizontal signaling of BCR with VEGFR2. In addition VEGFR2 signaling requires the expression of the BCR. These findings have profound implications for the potential side effects of EPO.
Abstract 5671: The Effects of Pharmacological PAI-1 Inhibition in Acute and Chronic Rejection in Murine Cardiac Allografts
Authors: Suzuki Jun-ichi , Ogawa Masahito , Muto Susumu , Yamaguchi Yoichi , Itai Akiko , Hirata Yasunobu , Nagai Ryozo , Isobe Mitsuaki 
Published: April 2024

Backgrounds: Acute rejection and graft arterial disease (GAD) in cardiac transplantation are enhanced by inflammation and thrombus formation. However, little is known about the effect of plasminogen activator inhibitor-1 (PAI-1) in heart transplantation. Thus, the objective was to clarify the role of PAI-1 in the progression of rejection.
Methods and Results: Murine hearts were heterotopically transplanted using major mismatch combinations for evaluation of acute rejection and class II mismatch combinations for the GAD. We performed administration of the specific PAI-1 inhibitor (IMD-1622) into murine recipients of cardiac allografts. Nontreated allografts of the major mismatch group were acutely rejected (n=6; 7.3±0.2 days), while the PAI-1 inhibitor prolonged their survival (n=6; 13.7±2.4 days, P < 0.05). Pathologically, severe myocardial cell infiltration (40.8±3.3 %) and fibrosis (44.5±2.8 %) were observed in untreated allografts, the PAI-1 inhibitor attenuated infiltration (25.8±1.9 %, p<0.05) and fibrosis (25.8±3.1 % p<0.05) in the class II mismatch group on day 60. Although severe GAD (luminal occlusion 28.6±6.4 %) was observed in untreated allografts, the PAI-1 inhibitor suppressed the development of neointimal formation (8.1±3.5 %, p<0.05). Immunohistochemically, CD8 and ICAM-1 were enhanced in nontreated allografts, while the PAI-1 inhibitor markedly attenuated expression of these factors. Zymography showed that increased gelatinase activity was observed in the non-treated allograft group, however, the PAI-1 inhibitor decreased the activity. RNAse protection assay revealed that PAI-1 inhibitor suppressed IFN-gamma compared with that of non-treated group.
Conclusion: The PAI-1 inhibitor is potent in the suppression of both allograft rejection and arterial disease because they are critically involved in the development of rejection through the suppression of inflammation.
Abstract 5793: Lower Extremity Peripheral Vascular Disease is an Independent Predictor of Adverse Outcomes After Percutaneous Coronary Intervention
Authors: Nanayakkara Shane S , Sharma Rahul P , Duffy Stephen J , Ajani Andrew E , Brennan Angela L , Reid Chris M , Andrianopoulos Nick , Shaw James A 
Published: April 2024

Background: A significant proportion of patients with coronary artery disease have coexistent peripheral vascular disease (PVD). Whether PVD is a predictor of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI) in the drug eluting stent era is not known.
Methods: Data was analysed from a total of 9110 patients from the Melbourne Intervention Group (MIG) database, a registry of patients undergoing PCI in Melbourne, Australia. Data was collected between April 2004 and July 2007 and analysed for baseline demographic data, traditional risk factors, procedural data and thirty day and twelve month major adverse cardiovascular events (MACE).
Results: Of the 9110 patients undergoing PCI, 632(6.9%) had PVD. Patients with PVD had an average age of 70.6 years, were more frequently diabetic (41.3% vs. 22.6%, p<0.01), were hypertensive (79.7% v 63.1%, p<0.01), and had higher lipid levels (82.5% v 70.6%). In the PVD group patients were more likely to have left main (2.4% vs. 0.7%, p<0.01) and ostial lesions(5.1% vs 3.4%, p=0.02) with no difference in acute procedural success between the 2 groups. 30 day MACE was higher in the PVD group (8.1% vs. 5% p<0.01) with a significant increase in early mortality. 12 month MACE was also more frequent in the PVD group (21% vs. 12.4%, p<0.01), with increased 12 month MI (9.8% vs. 4.3%, p<0.01) and mortality (8.6%v 3.5% p<0.01). On multivariate analysis, PVD independently increased the risk of 12 month MACE (OR 1.456, CI 1.07–1.99 p<0.01).
Conclusions: PVD is an independent predictor of adverse outcomes in patients undergoing PCI even correcting for traditional risk factors. In this study we found a significant increase in 30 day and 12 month mortality and MI in the PVD group, with diabetes and hypertension the most critical modifiable risk factors. Thus in patients undergoing PCI, the presence of peripheral vascular disease should be recognised as an additional factor in determining risk of cardiac events in the short and long term post PCI, with tighter diabetic control and lower blood pressure to be the primary targets of medical therapy in this group.