bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 9462: Endothelial Progenitor Cells Predict Five-Year Prognosis In Patients With Stable Angina Treated With Percutaneous Coronary Intervention
Authors: Pelliccia Francesco , Marazzi Giuseppe , Pasceri Vincenzo , Rosano Giuseppe , Mattioli Luigi , Greco Cesare , Gaudio Carlo 
Published: April 2024

Background. Endothelial progenitor cells (EPCs) have a pathogenetic role in stent restenosis after percutaneous coronary intervention (PCI). It remains undefined, however, if an association between numbers of EPCs at time of PCI and the subsequent long-term clinical outcome exists. To address this issue, we performed a pre-specified analysis of follow-up data of the PROCREATION (PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention) study.
Methods. A total of 155 patients (92 men, age 60±11 years) with stable angina treated with PCI were originally included in the PROCREATION study. All patients had flow cytometry the day before elective PCI in order to derive subpopulations of EPCs. After the index PCI, patients underwent 1-year control angiography and were then evaluated at 6-month intervals up to 5 years. The occurrence of major adverse cardiac events (MACE) was recorded in all patients.
Results. During the 5-year follow-up, all-cause death occurred in 16 patients (10%), cardiovascular death in 9 (6%), non fatal myocardial infarction in 6 (4%), and target vessel revascularization in 41 (26%). There were no significant differences in clinical and angiographic variables between patients with or without MACE. After adjusting for age, sex, left ventricular function, and number of diseased vessels, it was found that halving of numbers of CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells (i.e., progenitors of endothelial lineage) increased the risk of MACE by 75% (hazard ratio: 1.75; 95% confidence intervals: 1.1 to 2.8) and 66% (hazard ratio: 1.32; 95% confidence intervals: 0.9 to 2.3), respectively. Conversely, there were no relationships between outcome and numbers of CD14+/CD45+ cells (i.e., which play a role in angiogenesis via a paracrine effect) and CD105+/CD45-/CD34- cells (i.e., which have a receptor for transforming growth factor-beta).

Conclusions. Patients with stable angina treated with PCI who have a worse clinical outcome have lower numbers of circulating EPCs subtypes that are progenitors of endothelial lineage at time of the procedure. Assessment of EPCs at PCI can improve characterization of long-term prognosis. (ClinicalTrials.gov Identifier:
NCT01575431
)
Abstract 9660: The Impact of Anatomical Variation of the Brachial Artery for measuring Flow-mediated Vasodilation in Healthy Subjects and Patients with Cardiovascular Diseases
Authors: Fujii Yuichi , Higashi Yukihito , Hidaka Takayuki , Soga Junko , Idei Naomi , Fujimura Noritaka , Maruhashi Tatsuya , Mikami Shinsuke , Teragawa Hiroki , Kihara Yasuki 
Published: April 2024

Background: Measurement of flow-mediated vasodilation (FMD) is widely used for assessment of endothelial function. The purpose of this study was to evaluate the effect of anatomical variation of the brachial artery on FMD in healthy subjects and patients with cardiovascular diseases (CVD).
Methods and results: There was no significant difference in the ratio of existence of a double brachial artery between healthy subjects (6.1%, 13/213) and patients with CVD (6.5%, 11/169). In healthy subjects, FMD was larger in a single brachial artery than in large and small vessels of a double brachial artery (7.2±3.4% vs. 4.7±3.3% and 4.5±2.5%, P<0.01, respectively), while FMD was similar in large and small vessels of a double brachial artery. In patients with CVD, there were no significant differences in FMD among a single brachial artery, large vessel of a double brachial artery and small vessel of a double brachial artery (3.3±1.4%, 3.1±2.3% and 3.6±2.1%). FMD in a single brachial artery was smaller in patients with CVD than in healthy subjects (P<0.01). There were no significant differences in FMD in the large vessel of a double brachial artery between the two groups or in the small vessel of a double brachial artery between the two groups. Nitroglycerine-induced vasodilation was similar in all arteries in healthy subjects and patients with CVD. These findings suggest that when measuring FMD, we should take care about the existence of a double brachial artery, especially a double brachial artery in healthy subjects. FMD measured in a double brachial artery may be underestimated in healthy subjects.
Abstract 18172: Nicotine Accelerates the Expansion of Abdominal Aortic Aneurysms via a Matricellular Protein, Periostin
Authors: Azuma Junya , Otsu Rei , Taniyama Yoshiaki , Iwabayashi Masaaki , Morishita Ryuichi 
Published: April 2024

Abdominal aortic aneurysms (AAA) are more closely associated with cigarette smoking than any other tobacco-related disease except lung cancer. Periostin (PN) is a matricellular protein that is induced by mechanostress and regulates organ remodeling. Our previous study has shown that PN was significantly unregulated in early remodeling phase of AAAs and its ablation contributed to reduce AAA growth induced by angiotension ll (Angll). The purpose of the present study was to investigate the effect of nicotine on PN and its potential role in AAA disease progression.
PN-knockout (KO) mice were originally generated in our lab and crossed with ApoE-KO mice to establish ApoE/PN-double knockout (dKO) mice. Ang II (1.0 mg/kg/min) for 28 days or nicotine (7.0 mg/kg/min) for 42 days was administrated via osmotic minipumps for 24 >-wk-old male mice. Growth of AAAs was serially monitored by ultrasound imaging. The systolic blood pressure(BP)measured by tail cuff method was equivalent between ApoE-KO and ApoE/PN-dKO mice at baseline (101.4±7.3 vs 107.6±8.3mmHg, ns).
The BP response to Ang II or nicotine in ApoE/PN-dKO mice was also similar to that in ApoE-KO mice throughout the observation period (data not shown). In Ang II treated mice, the expansion rate of the aortic diameter (AD) was decreased significantly in ApoE/PN-DKO mice (n=10) over ApoE-KO mice (n=12) from day7 to 28day (239.3±43.4% vs 144.4±8.5% at day 28, p<0.05). Moreover the incidence of rupture and hematoma was significantly reduced in ApoE/PN-DKO mice at day 28 (60.0% vs 16.7% at day 28, p<0.05). In nicotine treated mice, the expansion rate of the AD was also diminished in ApoE/PN-DKO mice (n=5) over ApoE-KO mice (n=10) at day 42 (156.1±9.6 vs 113.9±4.0% at day 42, p<0.05). However no rupture or hematoma was observed in this treatment group.
The present study investigated the effect of nicotine on PN and their potential role in progressing AAAs. AngII had more potential induction of AAA rupture than nicotine in ApoE KO mice. Although the mechanism to develop AAA would be partially different between AngII and nicotine, the ablation of PN limited the AAA expansion in both AAA model. Antagonists against PN would lead to new therapeutic targets on a molecular basis to limit AAA progression related to cigarette smoking.
Abstract 18382: Stromal Cell Derived Factor-1Alpha Promotes C-kit+ Cardiac Stem/Progenitor Cell Quiescence Through Casein Kinase1Alpha and GSK3beta
Authors: Dimova Neviana , Wysoczynski Marcin , Rokosh Gregg 
Published: April 2024

A population of c-kit
+
cardiac stem/progenitor cells (CPSC) has been identified in the heart and shown to contribute to myocardial regeneration after infarction. Previously, we have shown the chemokine, stromal cell derived factor 1α (SDF1) is necessary for the myocardial response to infarction where chronic AMD3100 infusion exacerbated MI. Notably, AMD3100 increased CSPC proliferation.

The effect of SDF1 on CSPC proliferation was further investigated in primary cultures of magnetically sorted c-kit
+

CSPCs. SDF1 facilitated CSPC quiescenc by blocking cell cycle progression at the G0 to G1 transition. SDF1 decreased casein kinase 1α (CK1α) consequently attenuating β-catenin phosphorylation, destabilization, and degradation. Increased levels of β-catenin with SDF1 were effective, increasing TCF/LEF reporter activity. SDF downregulation of CK1α was dependent on proteasomal degradation and decreased mRNA expression. CK1α siRNA knockdown verified SDF1-dependent CSPC quiescence requires CK1α downregulation and stablilization of β-catenin. Conversely, β-catenin knockdown increased CSPC proliferation.
SDF1 also increased GSK3β Y216 phosphorylation responsible for increased activity. SDF1 mediated CK1α downregulation and increase in GSK3β activity affected cell cycle by downregulation of Bmi1, increased cyclin D1 phosphorylation, and decreased cyclin D1 levels.

In conclusion, SDF1 exerts a quiescent effect on resident c-kit
+

CSPCs by decreasing CK1α levels, increasing GSK3β activity, stabilizing β-catenin, and affecting regulation of the cell cycle through Bmi1 and cyclin D1. SDF1 dependent quiescence is an important factor in stem and progenitor cell preservation under basal conditions, however, with stress or injury in which SDF1 is elevated, quiescence may limit expansion and contribution to myocardial regeneration.
Abstract 18427: Impact of Medication on Quantification of Plasma MicroRNAs in Patients With Cardiovascular Disease
Authors: Kaudewitz Dorothee , Lee Regent , Willeit Peter , Zampetaki Anna , Morton Allison C , Warner Tim D , Storey Robert F , Channon Keith , Mayr Manuel 
Published: April 2024

Background:
MicroRNAs are small non-coding RNAs that are detectable in the blood. Circulating levels of microRNAs have been measured in various epidemiological studies, but the effects of medication are unclear. To address these uncertainties, we assessed how plasma microRNAs change in response to platelet inhibition and heparin administration. We also correlated plasma levels of microRNAs with existing markers of platelet activation.

Methods and Results:
92 microRNAs were assessed in a dose-escalation study with aspirin and prasugrel in healthy volunteers (n=11). Plasma levels of platelet microRNAs, such as miR-223, miR-191 and others decreased on platelet inhibition. Findings were confirmed by individual TaqMan qPCR assays and validated in an independent cohort of patients with symptomatic carotid stenosis (n=33).

In a cohort of patients on dual anti-platelet therapy 30 days post myocardial infarction (n=129), plasma levels of most platelet microRNAs were positively correlated to the VASP assay. Levels of miR-126 were also significantly associated with results from the VerifyNow P2Y12 aggregation assay. No association was observed with optical aggregometry with arachidonic acid or ADP.
When platelet-poor plasma was collected at different time points from patients undergoing PCI (n=20) or diagnostic angiography with (n=7) and without (n=10) heparin administration, heparin was found to have pronounced effects on the assessment of the exogenous C. elegans spike-in control (decrease by >3 cycles), which disappeared six hours after the heparin bolus. Normalisation of individual microRNAs with the average cycle threshold value of all microRNAs provided a suitable alternative to normalization with exogenous C. elegans spike-in control in this setting.

Conclusions:
Our studies provide evidence for a correlation of plasma microRNAs with commonly used methods in platelet testing. They also highlight that microRNA levels are sensitive to medication, in particular antiplatelet and anticoagulation therapy. This has to be taken into account when designing studies to investigate the relation of circulating microRNAs to cardiovascular disease.
Abstract 14355: Sinus Rhythm Prior to Catheter Ablation Positively Impacts Ablation Outcome in Non-Paroxysmal Atrial Fibrillation Patients
Authors: Mohanty Sanghamitra , Mohanty Prasant , Trivedi Chintan , Gianni Carola , Gunes Mahmut F , Gokoglan Yalcin , Bai Rong , Burkhardt John David , Sanchez Javier , Hranitzky Patrick , Gallinghouse G. J , Al-Ahmad Amin , Horton Rodney , Di Biase Luigi , Natale Andrea 
Published: April 2024

Background:
Catheter ablation of non-paroxysmal atrial fibrillation (NPAF) is associated with longer procedure times and lower long-term success rates than that of paroxysmal AF. We tested the hypothesis that NPAF patients entering the EP laboratory (lab) with sinus rhythm (SR) have shorter procedure time and better ablation-outcome than those with AF as the entry-rhythm.

Methods:
Total of 804 consecutive NPAF patients undergoing radiofrequency catheter ablation at our center were included in this prospective analysis. Based on the presenting rhythm in the EP lab, patients were classified into two groups; patients on SR (group 1, n=236, age 63±10 years, male 71%, LVEF 55.2±8.4, LA size 4.5±0.9 cm), patients in AF (group 2, n=568, age 64±10 years, male 69%, LVEF 54.4±11.4, LA size 4.6±0.6 cm). All patients were followed up for 38±6 months for arrhythmia recurrence by event recorder, ECG and Holter monitoring.

Results:
The baseline characteristics were not different between the groups. When comparing the procedural parameters between the groups, patients presenting with SR required significantly shorter radiofrequency time (64.1±30.7 min vs. 82.3±29.4 min in AF group, p<0.0001) and procedure times (143.9±91.2 min vs. 162.3±62.2 min in AF group, p=0.019).

At the end of follow-up, significantly higher recurrence rate was noted in those presenting with AF compared to patients on SR at the procedure; 264 of 568 (47%) vs. 80 of 236 (34%) respectively, log-rank p=0.002 (unadjusted hazard ratio 1.55 [1.17 - 2.05]) (figure).
After adjusting for AF type, age, gender, LA size, and LVEF in multivariable Cox model, patients presenting with AF at procedure were twice more likely to fail compared to those on SR (hazard ratio 1.91 (95% CI 1.19 to 4.15), p=0.001).

Conclusion:
Sinus rhythm prior to catheter ablation for non-paroxysmal AF decreases the duration of ablation and increases the long-term efficacy of the procedure.

Figure: Kaplan-Meier curve showing recurrence by study groups
Abstract 15426: Inflammasome-induced Signalling Mechanisms via Microparticles
Authors: Pfeifer Philipp , Felix Jansen , Zimmer Sebastian , Schild Katharina , Latz Eike , Franklin Bernardo , Nickenig Georg , Werner Nikos 
Published: April 2024

Introduction:
The inflammasome, a multi-protein signaling platform, has been shown to be an important mediator in the development of atherogenesis. Microparticles (MPs) are small membrane vesicles, which are released from apoptotic cells. Whether inflammasome activation leads to the release of MPs by vascular cells is unknown.

Hypothesis:
Inflammasome-activation in vascular cells leads to microparticle release. These microparticles contain components of the inflammasome and exert functional effects on other vascular cells.

Methods:
EMP (endothelial microparticles) and MMP (monocytic microparticles) were quantified by flow cytometry using TruCount tubes. Inflammasome-activation was investigated by IL-1β ELISA and immunoblotting. The latter was also used to determine EMP content. Viability Assay was performed to test cell-viability and Scratch assay to examine effects of EMP on migration and proliferation of vascular cells.

Results:
Human coronary artery endothelial cells (HCAEC) and monocytes were primed with LPS and subsequently stimulated with either ATP or Nigericin, two established inflammasome activators. MP release was quantified by flow cytometry using TruCount tubes. Stimulation of HCAEC and monocytes with both Nigericin and ATP resulted in a time-dependent release of MPs.

Inflammasome-activation in HCAEC was confirmed by the release of IL-1β into the cell supernatant and immunoblotting against Caspase-1. Immunoblotting also showed that inflammasom-activated HCAEC and the associated EMP contain pro-Caspase-1, active Caspase-1 and NALP-3.
Inoculation of HCAEC with EMP, derived from HCAEC stimulated with Nigericin, lead to a rapid and significant cell death and reduced cell migration/ proliferation shown by Viability Assay and Scratch Assay, respectively.

Conclusions:
We show for the first time that Nigericin and ATP, two established inflammasome activators, lead to inflammasome activation and release of microparticles by vascular cells. Furthermore, we could demonstrate that these microparticles contain pro-Caspase-1, mature-Caspase-1 and NALP-3 and that they cause cell death accompanied with reduced cell migration and proliferation.
Abstract 15635: Consumption of Aspirin and Naproxen by Platelet Donors and the Quality of Platelet Transfusion
Authors: Li Xuanwen , Fries Susanne , Sachais Bruce S , Cuker Adam , Blair Ian A , Grosser Tilo 
Published: April 2024

Over-the-counter pain killers are amongst the most frequently consumed drugs world-wide. Individuals who self-report ingesting aspirin or aspirin containing drugs within the preceding 48-72 hours - depending on regional practice - are excluded from platelet donation, given the assumed platelet functional inhibition due to irreversible acetylation of platelet cyclooxygenase-1 (COX-1) by aspirin and the consequent suppression of thromboxane formation. Other nonsteroidal anti-inflammatory drugs, which bind COX-1 tightly enough to cause long acting platelet inhibition, such as naproxen, may also impact the quality of platelet preparations for transfusion but are not typically exclusionary. The prevalence of functionally relevant exposure of platelet donors to aspirin and naproxen is unknown.
We used sensitive and specific mass spectrometry methods to quantitate the acetylation of platelet COX-1 by aspirin and platelet protein binding of naproxen in platelet transfusion units as indices of donor exposure to these drugs. Platelet thromboxane formation was assessed as a functional parameter. We screened single-donor apheresis platelet units transfused at the Hospital of the University of Pennsylvania.
Over 30 % (71 out of 235) of the analyzed platelet units showed evidence of aspirin exposure ranging from residual COX-1 acetylation after an appropriate washout period to complete acetylation suggestive of recent aspirin exposure. Approximately 7% (16 out of 235) of the platelet units showed complete COX-1 acetylation and inhibition of thromboxane formation. More than 15% (22 out of 143) of analyzed platelet units showed high naproxen concentrations that were associated with depression of thromboxane formation.
The prevalence of aspirin and naproxen consumption by platelet donors is as high as would be expected in the general population and results in transfusion of inhibited platelets with suppressed thromboxane formation.
Abstract 13748: A Disintegrin and Metalloproteinase 17 Deletion in Smooth Muscle Cell Transiently Suppresses Angiotensin II Mediated Hypertension
Authors: Shen Mengcheng , Morton Jude , Davidge Sandra T , Kassiri Zamaneh 
Published: April 2024

Introduction:
A disintegrin and metalloproteinase-17 (ADAM17) proteolytically releases membrane-bound growth factors and cytokines. Hypertension is associated with remodeling, hypertrophy and hyperplasia of smooth muscle cells (SMCs). ADAM17 has been reported to mediate Angiotensin II (Ang II)-induced SMC hypertrophy. We investigated the role of smooth muscle cell ADAM17 in Ang II-induced hypertension.

Hypothesis:
Smooth muscle cell ADAM17 deficiency suppresses Ang II-induced hypertension.

Methods:
SMC-specific ADAM17-deficient mice (

Adam17
flx/flx
/SM22Cre

;

Adam17
SMC-Cre

), and littermate controls (

Adam17
flx/flx

) received Ang II or saline (Alzet pumps, 1.5 mg/kg/d; 4 wks). Blood pressure was measured in conscious mice before and 4 wks after Ang II infusion (Telemetry). Vascular function (vasoconstrictor/dilator response), circumferential wall stress/strain were assessed in second order mesenteric arteries
ex vivo
at 2 wks after Ang II/saline infusion.

SMCs were isolated from either genotype (enzyme dispersal method). SMC proliferation (BrdU incorporation), migration (scratch assay) and apoptosis (Annexin V/7-AAD staining, Flow Cytometry) were assessed (±Ang II). Activation of signaling pathways (phospho/total EGFR, Akt and ERK1/2), HB-EGF were assessed by Western blot.

Results:

Adam17
SMC-Cre

mice exhibited suppressed hypertension in the 1
st
week of Ang II infusion (reduced systolic, diastolic & MAP). However, by the 2
nd
week, systolic and diastolic BP rose to similar levels as

Adam17
flx/flx

mice and remained similar.
Ex vivo
analyses revealed similar acute vasoconstrictor/dilator responses, and comparable wall stiffness in both genotypes; but the Ang II-induced increase in wall thickness was not observed in

Adam17
SMC-Cre

group.

ADAM17-deficient SMCs showed reduced Ang II-induced proliferation, migration, and activation of HB-EGF and ERK1/2. A time-course study revealed delayed Ang II-mediated EGFR activation in ADAM17-deficient SMCs (@24 hrs vs 30 min).
End organ damage, hypertrophy and fibrosis in the heart and kidneys, were comparable.

Conclusions:
ADAM17 deficiency in SMCs causes a transient reduction in Ang II-induced hypertensive response, possibly due to delayed activation of the EGFR pathway.
Optimal Degree of Balloon-Expandable Transcatheter Valve Oversizing in Patients With Borderline Aortic Annulus Measurements: Insights From a Multicenter Real-World Experience
Authors: Panagides Vassili , Cheema Asim N. , Urena Marina , Nombela-Franco Luis , Veiga-Fernandez Gabriela , Vilalta Victoria , Regueiro Ander , Del Val David , Asmarats Lluis , del Trigo Maria , Serra Vicenç , Munoz-Garcia Antonio , Rezaei Effat , Himbert Dominique , Tirado-Conte Gabriela , de la Torre Hernandez José M. , Fernandez-Nofrerias Eduard , Cepas-Guillén Pedro L. , Alfonso Fernando , Gutierrez-Alonso Lola , Oteo Domínguez Juan Francisco , Belanech Yassin , Paradis Jean-Michel , Mesnier Jules , Rodés-Cabau Josep 
Published: April 2024

Background:
The potential benefit of using larger or smaller transcatheter heart valves (THV) in patients with borderline aortic annulus measurement (BAM) remains uncertain. The objective of this study was to evaluate the clinical outcomes associated with the selection of larger or smaller THV in the context of BAM.

Methods:

This was a multicenter observational study including patients who underwent transcatheter aortic valve replacement with the SAPIEN 3 or SAPIEN 3 Ultra-valve systems (Edwards Lifesciences, Irvine, CA) from April 2014 to June 2021. BAM was defined according to the manufacturer sizing chart and included the following annulus areas: 314 to 346, 400 to 430, 500 to 546 mm
2
. A 1:1 propensity score matching was used to compare outcomes of patients with larger or smaller THV.

Results:

From a total of 2467 patients, BAM was identified in 852 patients (34.5%). A larger and smaller THV was selected in 338 (39.7%) and 514 patients (60.3%) patients, respectively. The choice of a larger THV was associated (before and after propensity matching) with a higher risk of new-onset left bundle branch block (HR, 2.25 [95% CI, 1.39–3.65;
P
=0.001) and permanent pacemaker implantation (HR, 1.86 [95% CI, 1.11–3.09];
P
=0.016) without any impact on gradients or the risk of moderate or severe paravalvular regurgitation at discharge (HR, 0.78 [95% CI, 0.41–1.45];
P
=0.427). The risk of periprocedural complications such as aortic rupture and tamponade was low (<1%) and similar between groups.

Conclusions:
In patient with BAM, selecting a larger SAPIEN 3/Ultra THV increased the risk of conduction disturbances without any benefit on valve hemodynamics and clinical outcomes.