bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5037: Phosphorylation of eNOS Corrects Diabetic Vascular Dysfunction and Improves Outcome to Stroke
Authors: Li Qian , Atochin Dmitriy , Kashiwagi Satoshi , Earle John , Wang Annie , Sessa William , Huang Paul 
Published: April 2024

Background: While diabetes is associated with diminished vascular NO levels, the precise mechanisms of diabetic endothelial dysfunction are not known. We hypothesized that deficient eNOS S1179 phosphorylation plays a key role in diabetic vascular abnormalities, and that increasing S1179 phosphorylation may improve endothelial function. To test this hypothesis, we created eNOS knock-in mice that carry a S1179D mutation in the eNOS gene, resulting in the generation of a phosphomimetic form of eNOS with increased enzymatic activity and NO generation. We bred these animals to db/db mice to obtain S1179D-db/db mice to test whether modulation of the S1179 phosphorylation site could overcome diabetic vascular dysfunction, and whether this could affect stroke size in vivo.
Experimental Procedures: Adult male mice were anesthetized by 30 % oxygen, 70 % nitrous oxide, and 1.5 % isoflurane. Body temperature was maintained at 36–37°C. Vessel reactivity studies were performed on isolated pressurized carotid arteries. For stroke studies we used the middle cerebral artery occlusion with subsequent reperfusion by filament with Laser Doppler cortical blood flow monitoring. Mice were examined for neurologic deficits 24 hours after stroke. Infarct sizes were determined by the indirect method by 2,3,5-triphenyltetrazolium chloride staining. Statistical analysis was performed with t-test.
Results: Db/db mice showed normal levels of total eNOS, while S1179 phospho-eNOS was diminished. Db/db mice are hypertensive compared with wild-type (WT) mice (116±4 vs 93±3 mm Hg, mean± SEM). The eNOS S1179D mutation normalizes the blood pressure of db/db mice (92±5 mmHg). Carotid artery vasodilation to ACh was impaired in db/db mice (EC50 43.4±6.1 nM) compared with WT mice (16.3±2.9 nM) and S1179D-db/db mice (26.6±4.2 nM). Db/db mice show a larger stroke (100±7 mm3) than do WT (65±7 mm3) and S1179D-db/db mice (80±4 mm3, P<0.05). This was associated with a functional improvement in the neurologic deficit.
Conclusion: Our results establish eNOS phosphorylation as an important cause of vascular dysfunction in db/db mice, and suggest eNOS phosphorylation as a novel target for the treatment and prevention of diabetic vascular disease and stroke.
This research has received full or partial funding support from the American Heart Association, National Center.
Abstract 5132: Serum Pentraxin 3, Matrix Metalloproteinase 9 and Intraplaque Hemorrhage in Carotid Atherosclerosis
Authors: Moriguchi Emilio , Narvaes Luciane , Silvello Daiane , Albuquerque Luciano , Meurer Luise , Santos Kátia , Rohde Luis 
Published: April 2024

Background - Carotid intraplaque hemorrhage (IPH) is a marker of atheroma instability. In the present study, we evaluated the potential association between serum levels of pentraxin 3 (PTX3, a novel marker of vascular inflammation) and matrix metalloproteinases (MMPs) with
in vivo
assessment of IPH by high-resolution magnetic resonance imaging (MRI).

Methods and Results - Consecutive patients submitted to carotid endarterectomy underwent high-resolution MRI; independent evaluation of neurological symptoms; histological analysis and measurement of serum PTX3, MMP-3 and MMP-9. IPH was determined non-invasively by the presence of a hyperintense signal on MRI. Eighty-two predominantly male (65%) and hypertensive (89%) patients (67±9 years-old) were studied. MR angiography identified 19(23%) patients with 50 – 69% stenosis, 23(28%) with 70 –90% stenosis, and 40(49%) with > 90% stenosis. High-resolution MRI depicted a hyperintense signal suggestive of intraplaque bleeding in 48 (58.5%) subjects. No usual clinical characteristic was predictive of the hyperintense signal on MRI (all p values >0.10). Serum PTX3 and MMPs levels were similar in different degrees of carotid stenosis assessed by MR angiography, but were significantly augmented in patients with signs of IPH on MRI and on histological analysis (all p values <0.05). We observed a strong positive association between PTX3 and MMP-9 levels (r=0.76; p<0.0001) and a weak to moderate association between hs-C-reactive protein and PTX3 (r=0.40; p=0.0002) and MMP-9 (r=0.35; p=0.001). In a multivariate logistic regression model adjusted for potential blood-derived markers, clinical neurological instability was the only variable independently associated to MRI-based IPH.
Conclusions - MRI-based IPH identified neurologically unstable patients, with increased levels of PTX3 and MMP-9, regardless of the degree of carotid luminal stenosis.
Abstract 5545: An Experimental Study With Microwave Thermography for the Assessment of Atherosclerotic Vascular Disease
Authors: Toutouzas Konstantinos , Synetos Andreas , Drakopoulou Maria , Tsiamis Eleftherios , Karanasos Antonis , Michelongona Archontoula , Grassos Haris , Stefanadi Elli , Siores Elias , Stefanadis Christodoulos 
Published: April 2024

Background: Intravascular thermography (IVT) is the only method currently available, which can measure heat generation from atheromatic plaques indicating local inflammation. Thermal heterogeneity of the atheromatic plaque has been correlated with mophological characteristics of the culprit lesion in patients with coronary artery disease. Microwave radiometry (MR) is a new non-invasive method. We investigated whether thermal heterogeneity measured by MR is correlated with IVT findings in an experimental model of atherosclerotic disease.
Methods: Microwave radiometry (RTM-01-RES system) was applied noninvasively in 18 atherosclerotic segments of the aorta (3 segments, 5cm long in 6 rabbits) that were clearly separated from each other, as well as in 18 control segments. Microwave radiometry measures natural electromagnetic radiation from the internal tissues at microwave frequencies that is proportional to the temperature of tissue. The system consists of an internal temperature sensor with the antenna, a skin temperature sensor and the data processing unit. The accuracy of measuring the internal temperature of the device is±0.2°C and the depth of temperature detection is 1–7 cm. Thereafter, IVT was performed in the same segments. For both techniques temperature difference (ΔT) was calculated by subtracting the mean temperature of proximal healthy vessel wall from the maximal temperature of each segment.
Results: Thermal heterogeneity was detected by both methods in the rabbits with the high atherogenic diet. Microwave radiometry detected that ΔT of the atherosclerotic aortas was significantly higher compared to the ΔT of the controls (0.98±0.27 °C versus 0.40±0.14°C, p<0.001). These findings were confirmed by the measurements acquired by IVT. Mean temperature difference was 0.07±0.01 °C for the atherosclerotic aortas versus 0.02±0.01°C, (p<0.001) for the control group. The segments that had the highest ΔT were those that were recognized in angiography as having significant atheromatosis.
Conclusion: Microwave radiometry is the first non-invasive method for detection of local inflammatory activation in arterial segments in an experimental model. Further studies in humans should be performed for the evaluation of this method.
Abstract 5755: The Role of Adhesion and Migration of Stimulated Multipotent Stromal Cell With EGF in Vasculogenesis in Type 2 Diabetes
Authors: Amin Ali H , Elmageed Zakaria Y Abd , Partyka Megan , Ismail Mohammed F , Elazeik Osman Y , Belmadani Souad , Matrougui Khalid 
Published: April 2024

Background: Chronic tissue ischemia due to defective vascular perfusion is a marker of peripheral artery disease for which minimal therapeutic options exist. Thus, type 2 diabetes is characterized with altered stem cells and vasculogenesis. Because of the capability of stem cells to differentiate into vascular cells and the importance of epidermal growth factor (EGF) in angiogenesis, their critical role in the treatment of type 2 diabetic patients with ischemia peripheral artery disease may be as prophylactic agents preventing tissue damage by stimulating vasculogenesis. Therefore we determined if multipotent stromal cells (MSC) tagged with enhanced green fluorescent protein (EGFP) stimulated with or without exogenous EGF would improve vasculogenesis in ischemia hind limb of type 2 diabetic (db−/db−) mice.
Methods and Results: Isolated bone marrow from db−/db− mice showed an increase in oxidative stress and reduction in Akt compared to control. Ischemia was induced in the hind limb of db−/db− mice and control for 28 days. EGFP-MSC stimulated with or without exogenous EGF (10 ng/ml) for 24 hr were locally injected in the mice hind limb once a week for 4 weeks. After 4 weeks, blood flow measured with MoorLDI-Laser and angiogenesis assessed with X-ray were completely recovered in control mice compared to db−/db− mice. Interestingly db−/db− mice display a significant improvement of blood flow (60% and 96%) and vasculogenesis (61% and 98%) when treated with MSC or MSC pre-stimulated with exogenous EGF, respectively. Western blot analysis on hind limb muscles revealed an increase in phosphorylated Akt and VEGF receptor in db−/db− mice injected with MSC or MSC+EGF compared to non-treated db−/db− mice. Fluorescent microscopy images indicate that EGFP-MSCs differentiate into new microvessels. In vitro studies showed that adhesion and migration of MSC on cultured microvascular endothelial cells were elevated when MSC were pre-stimulated with EGF compared to non-stimulated MSC.
Conclusion: Our novel data provide evidence that in type 2 diabetes, MSC stimulated with EGF are able to significantly improve, better than MSC alone, the formation of microvessels in response to ischemia.
Abstract 5763: GP IIb/IIIa Inhibitors During Primary Percutaneous Coronary Intervention for STEMI: A Meta-Analysis of Randomized Controlled Trials
Authors: Tamhane Umesh U , Meier Pascal , Chetcuti Stanley , Grossman P. Michael , Gurm Hitinder S 
Published: April 2024

Background: Earlier meta analyses demonstrated a survival benefit with adjunctive GP IIb/IIIa inhibitors (GPI) during primary percutaneous interventions (pPCI) for STEMI. Recent pPCI trials evaluating the role of GPI have demonstrated conflicting results. We performed a comprehensive meta-analysis to evaluate the role of adjuvant GPI therapy in patients undergoing pPCI.
Methods: Our meta-analysis included 15 randomized trials (n= 11407 patients) comparing adjunctive GPI therapy with heparin or bivalirudin in patients undergoing pPCI for STEMI. Summary odds ratios for safety and efficacy endpoints at 30 days were calculated using random-effects models.
Results: There was no significant difference in the incidence of 30-day mortality (Odds ratio [OR] 0.90, 95% CI 0.65–1.23, p = 0.49), reinfarction (OR 0.84, 95% CI 0.61–1.15, p = 0.27) or stroke (OR 0.68, 95% CI 0.35–1.30, p = 0.25). GPI therapy was associated with a significant reduction in rates of target vessel revascularization (OR 0.67, 95% CI 0.53 – 0.85, p = 0.001) and stent thrombosis (OR 0.51, 95% CI 0.32 – 0.83, p = 0.006). The risk of major bleeding (OR 1.72, 95% CI 1.39 –2.14, p< 0.001) and thrombocytopenia (OR 2.2, 95% CI 1.63–2.98, p< 0.001) was significantly increased in the GPI regimen.GPI therapy would prevent approximately 9 ST at the cost of 10 major bleeding episodes for every 1000 STEMI patients.
Conclusion: Adjuvant GPI therapy is not associated with improved survival compared to control therapy in STEMI patients undergoing pPCI. It significantly reduced ST and TVR at the cost of increase in major bleeding and thrombocytopenia.
Abstract 8300: SkM1 Gene Transfer Into Canine Ventricular Myocardium Decreases the Threshold Potential for Action Potential Initiation
Authors: Sosunov Eugene A , Boink Gerard J , Shlapakova Iryna N , Kryukova Yelena , Danilo Peter , Anyukhovsky Evgeny P , Cohen Ira S , Robinson Richard B , Rosen Michael R 
Published: April 2024

Introduction:
We have previously shown that combined HCN2/SkM1 gene expression in canine left bundle branch (LBB) results in a biological pacemaker having a faster rate than that based on HCN2 alone. We now tested the hypothesis that expressing Nav1.4 channels (encoded by the SkM1 gene) decreases the threshold potential (TrP) for action potential (AP) initiation. Thus, in the LBB expressing Nav1.4, the same slope of phase 4 depolarization should bring membrane potential to TrP faster, resulting in a more rapid automatic rate. We now tested this hypothesis in left ventricular subepicardial (LV) preparations suitable for current injection and TrP measurement.

Methods:
Adenoviral constructs of HCN2, SkM1 or HCN2/SkM1 were implanted into canine anterior LV. At 7d, myocardial fascicles (~0.5 mm diameter, 6-10 mm long) were isolated from injected sites and transferred to a tissue bath having 2 compartments separated by a plastic membrane with a hole permitting passage of the preparation. Transmembrane potential was recorded by microelectrodes. Preparations were driven at 1 Hz and every 10th stimulus was substituted by a 30 ms pulse of extracellular depolarizing current. The magnitude of depolarizing current was gradually increased until AP was initiated and TrP recorded.

Results:
For regularly paced AP, there were no differences in maximum diastolic potential (MDP) among groups whereas maximum upstroke velocity (V
max
) was higher in SkM1 and HCN2/SkM1 than in HCN2 (Table, *
P
<0.05 vs HCN2). TrP was significantly more negative and V
max
at TrP was higher in SkM1 and HCN2/SkM1 than in HCN2 (Table, *
P
<0.05 vs HCN2).

Conclusions:
Expression of Nav1.4 Na+ channels can accelerate the rate of HCN2 based biological pacemakers by decreasing TrP for AP initiation.
Abstract 9501: Key Role of Low High Density Lipoprotein Cholesterol for the Association of the Metabolic Syndrome with Inflammation in Patients with Peripheral Arterial Disease
Authors: Rein Philipp , Saely Christoph H , Boehnel Christian , Beer Stefan , Vonbank Alexander , Kiene Veronika , Drexel Veronika , Drexel Heinz 
Published: April 2024

The association of the metabolic syndrome (MetS) and of the individual MetS stigmata with inflammation in patients with peripheral arterial disease (PAD) has not been investigated yet and is adressed in the present study.
We enrolled 410 consecutive patients who underwent routine duplex sonography for the evaluation of suspected or established PAD Fontain stages I-III and in whom PAD was verified sonographically. According to National Cholesterol Education Programme Adult Treatment Panel III criteria, the MetS was defined in the presence of at least 3 out of the 5 quantitatively defined criteria large waist circumference, low HDL cholesterol, high triglycerides, high blood pressure, and elevated fasting glucose. In univariate analyses, CRP was higher in patients with the MetS (n=200) than in those who did not have the MetS (0.94±1.88 vs. 0.56±1.18 mg/dl; p=0.001), and also was higher in patients who fulfilled the large waist (0.93±1.93 vs. 0.59±1.16 mg/dl; p = 0.009) and the low HDL criteria (1.10±1.66 vs. 0.61±1.52 mg/dl; p<0.001) than in those who did not. Importantly however, after adjustment for gender, smoking, BMI and LDL cholesterol by means of ANCOVA only the low HDL cholesterol criterion (F=6.06; p=0.014) remained significantly associated with CRP. The significant and independent association of low HDL with CRP was confirmed after additional adjustment for all other MetS traits (F=7.76; p=0.006).
We conclude that among patients with sonographically proven PAD, low HDL cholesterol drives the association between the MetS and subclinical inflammation. This observation is well in line with the paramount role of low HDL cholesterol as a marker of cardiovascular risk.
Abstract 18603: Estrogen Plays a Protective Role in Advanced Heart Failure by Regulating Target Genes of miR-129-5p Suppressing Cardiac Fibrosis
Authors: Sharma Salil , Iorga Andrea , Nadadur Rangarajan D , Eghbali Mansoureh 
Published: April 2024

Background: Moderate cardiac fibrosis has been reported in advanced heart failure (HF) induced by pressure overload in mice. We have previously shown that short term estrogen(E2) therapy starting after the advanced HF can rescue HF. E2 has been shown to reverse fibrosis through estrogen receptor beta(ERb). Here, we explored whether E2 can suppress cardiac fibrosis by inducing miR-129-5p expression through ERb mediated mechanism and verified its key target genes.
Methods and results: We used transaortic constriction to induce HF in male mice, and once the ejection fraction (EF) reached ∼30%, one group of animals was sacrificed (HF group), and the other group received 17b-estradiol via a subcutaneous pellet implant (0.012mg/pellet, n=16) (E2 group) for 10 days. Sham-operated mice served as CTRL. Serial echocardiography was performed to monitor cardiac structure and function. Short-term E2 treatment rescued pressure overload-induced decompensated HF in mice by restoring the EF from 33.17±1.12% to 53.05±1.29(p <0.001). E2 also decreased both interstitial and prevascular fibrosis in HF. MicroRNA microarray analysis and qPCR validation revealed that miR-129-5p is upregulated ∼2 fold in E2 group compared to HF group. Interestingly, miR-129-5p showed no significant change in E2 versus CTRL suggesting altered miR-129-5p expression in HF was restored to CTRL group by E2 treatment. Treatment of HF with ERb agonist (DPN), but not ER-alpha agonist (PPT), also resulted in the upregulation of miR-129-5p indicating the estrogen mediated induction of miR-129-5p is possibly mediated through ERb. In vitro, angiotensin II treatment significantly downregulated miR-129-5p expression in fibroblasts which was restored by estrogen and DPN but not by ERb antagonist (PHPT) further confirming the role of ERb in regulating miR-129-5p. In vitro, over-expression of miR129-5p in fibroblasts resulted in the significant down-regulation of many potential pro-fibrotic target genes including COL1A, PDGFA, GREM1 and the transcription factor SOX4.

Conclusion:
Our data strongly suggests that estrogen treatment during HF induces miR-129-5p likely through ERb. Mechanistically, miR-129-5p represses fibrosis by targeting key component genes associated with cardiac fibrosis.
Abstract 18611: Transcatheter Aortic Valve Implantation Reduces Central Sleep Apnea in Patients with Severe Aortic Stenosis
Authors: Linhart Markus , Fistéra Rebecca , Pabst Stefan , Ghanem Alexander , Sinning Jan-Malte , Hammerstingl Christoph , Springmann Karin , Werner Nikos , Nickenig Georg , Skowasch Dirk 
Published: April 2024

Introduction
While the association between congestive heart failure and central sleep apnea (CSA) is well described, the role of sleep disordered breathing (SDB) and particularly CSA in valvular heart disease is unclear. We evaluated 67 patients with high-grade aortic stenosis and high preoperative risk for the prevalence of SDB before and after transcatheter aortic valve implantation (TAVI).

Methods 67 consecutive patients that were eligible for TAVI were underwent an overnight polygraphy (Embletta ® Device, Embla). Clinical, echocardiographic and invasive data were collected. SDB was defined as an apnea-hypopnea-index (AHI) >5/h. In 31 patients that to date performed the 3 months follow-up, monitoring was repeated and compared to the baseline status.
Results Prevalence of SDB was 61% with a clear predominance of CSA (43%, table 1). In the 3 months follow-up that was completed by 31 patients so far, significant improvement in AHI, AI central, LVEF, NYHA class and NT pro-BNP was seen (table 2). There was a highly significant inverse correlation of NT pro-BNP with LVEF (r=-0.72, p<0.001) but not with severity of CSA (r=0.19, p=0.13). 18 patients died before the 3 months follow-up.
Conclusion We can show a high prevalence of SDB, in particular of CSA, in this patient cohort. There is a highly significant improvement of sleep apnea in the CSA subgroup after TAVI, which is independent of left ventricular function and NT pro-BNP.
Abstract 18683: Outcomes of Patients Presenting with Acute Type A Aortic Dissection in the Setting of Prior Cardiac Surgery: An Analysis from the International Registry of Acute Aortic Dissection
Authors: Teman Nicholas , Peterson Mark D , Russo Mark J , Ehrlich Marek P , Myrmel Truls , Upchurch Gilbert R , Greason Kevin , Fillinger Mark , Forteza Alberto , Deeb Michael G , Montgomery Daniel G , Eagle Kim A , Isselbacher Eric M , Nienaber Christoph A , Patel Himanshu J 
Published: April 2024

Introduction: Prior cardiac surgery can complicate the clinical presentation, diagnosis, and management of patients with type A aortic dissection (TAAAD). This report from the International Registry of Acute Aortic Dissection (IRAD) examines this hypothesis.
Methods: 352 of 2289 TAAAD patients (15.4%) enrolled in IRAD had cardiac surgery prior to dissection, including coronary artery bypass grafting (CABG, 34.6%), aortic or mitral valve surgery (38.4%), aortic surgery (44.7%), and other cardiac surgery (18.1%).
Results: Comparative differences in baseline demographics, clinical presentation, and management time are shown in Table 1. Patients with prior cardiac surgery were more likely to undergo CABG (p=0.006) or mitral valve replacement (p=0.001) at the time of dissection repair. Total cardiopulmonary bypass time was higher in patients with prior cardiac surgery (p<0.001); no difference was seen in cardiac arrest time (p=0.113) or cerebral ischemia time (p=0.286). In-hospital mortality was significantly higher for patients with prior cardiac surgery (33.5% vs. 24.0%, p70 (RR1.58, 95% CI 1.25-1.99), and medical management of acute dissection (RR 4.79, 95% CI 3.62-6.34). Kaplan-Meier analysis is shown in Figure 1.
Conclusion: Prior cardiac surgery not only delays presentation and diagnosis of acute type A dissections, but is also an important adverse risk factor for early and late mortality.