bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 52: The Gut Microbiome Alters Susceptibility to Coronary Inflammation in Kawasaki Disease
Authors: Yeung Rae S , Chan Daniel , Duong Trang T 
Published: July 2021

The gut microbiome has been shown to have immunomodulatory capabilities, and changes in the composition of the microbiome have altered the pathogenesis of inflammatory diseases. In this study, we sought to investigate the effects of the microbiome on the pathogenesis of Kawasaki Disease (KD) using the Lactobacillus cell wall extract (LCWE)-induced coronary arteritis model. Using qPCR on mouse fecal samples, we quantified bacterial communities through the 16S rRNA gene. Animals originating from the same supplier where housed in two independent facilities. There were marked elevations in Bacteroides, Bifidobacteria, Lactobacillus and segmented filamentous bacteria (SFB) and decrease in Clostridia in Facility A compared to Facility B. The transition to the newer Facility B resulted in a reduction in disease induction by LCWE to 26% (25/95), compared to 50% (35/70) at Facility A.
Addition of antibiotics to the drinking water to deplete the microbiome reduced disease incidence to 40% (2/5) of mice housed at Facility A compared to 100% (5/5) of untreated mice, suggesting that components of the microbiome are necessary to exacerbate inflammation. To address whether the gut microbiome was sufficient to support disease susceptibility, the cecal contents of the susceptible mice at A were gavaged into the less susceptible mice at B. Recipients of the cecal contents from Facility A had an increased disease incidence of 91% (10/11) compared to 60% (6/10) in control mice which received cecal contents from mice housed in Facility B.
We also report elevated levels of IL-17 in the serum of SFB-colonized mice. SFB, known to exacerbate several models of autoimmunity, was completely absent in mice housed at Facility B. Interestingly Th17 and its associated cytokine IL-17 have been associated with acute KD, but its role in pathogenesis remains unclear. Th17 cells have been implicated in autoimmunity, and are also important players in gut homeostasis. Our data provide evidence for the role of the gut microbiome in modulating the immunopathogenesis of KD, pointing to the important interactions of commensal and pathogenic factors as determinants of disease.
Abstract 10980: Myositis, Myocarditis, and Mitochondria: A Thread Connecting the Myofilaments
Authors: Houston Brian A , Hsu Steve , Halushka Marc , Gelber Allan , Judge Daniel 
Published: July 2021

A 67 year old man presented in 2013 with new heart failure symptoms. A curious past medical history prompted pursuit of an etiologic diagnosis. In 2006, he developed weakness and elevated creatine kinase (CK). Muscle biopsy was consistent with a necrotizing myopathy, and a serologic panel of auto-antibodies was unrevealing. He was started on prednisone. In 2011, he presented with atypical chest pain, and ECG demonstrated frequent atrial and ventricular ectopy. Both troponin-I and CK were elevated. Cardiac CT angiography ruled out obstructive coronary disease, and he remained stable until the onset of heart failure symptoms prompted his current admission. On examination, the patient had evidence of proximal muscle weakness and atrophy. His jugular venous pulse was elevated, and auscultation revealed an S3 gallop. Troponin (0.35 ng/mL) and CK (776 U/L) were both elevated and remained consistently so. Echocardiography revealed severely reduced left ventricular function.
Search for a unifying diagnosis prompted review of his myositis panel whereupon immunoprecipitation bands characteristic for anti-mitochondrial antibodies were discovered. Serologies for anti-mitochondrial antibodies returned positive. His plasma lactate was elevated with a normal pyruvate level, mimicking the changes seen in inborn errors of mitochondrial function. Cardiac magnetic resonance imaging showed patchy gadolinium enhancement in the mid-myocardium of the septum and lateral wall in a non-coronary distribution and no perfusion abnormalities. Endomyocardial biopsy established the presence of myocarditis, confirming the diagnosis of anti-mitochondrial antibody-associated myocarditis and myositis.
Along with a beta-blocker and diuretic (he experienced worsening renal insufficiency on low-dose ACE inhibitor), we initiated azathioprine at 50 mg up-titrating to a dose of 150 mg daily over several weeks. The patient reported no recrudescence of heart failure symptoms. Echocardiogram three months later revealed improved left ventricular function, and his CK and troponin-I levels normalized. In cases of idiopathic myositis and myocarditis, anti-mitochondrial antibodies may provide a unifying diagnosis and significantly alter management and prognosis.
Abstract 14077: Use of Cardiac Troponin I to Identify Acute Myocardial Infarction in Patients With Impaired Renal Function
Authors: von Jeinsen Beatrice , Tzikas Stergios , Palapies Lars , Zeller Tanja , Bickel Christoph , Lackner Karl J , Baldus Stephan , Blankenberg Stefan , Muenzel Thomas , Zeiher Andreas M , Keller Till 
Published: July 2021

Introduction:
Cardiac troponins are the gold standard to diagnose acute myocardial infarction (AMI). Troponin I (TnI) levels are known to be increased in patients with chronic kidney disease (CKD) irrespective of an AMI. The established diagnostic TnI cut-off to detect AMI is calculated based on a healthy reference population and might not be representative for CKD patients.

Hypothesis:
The aim of this study was to investigate TnI levels in patients with and without CKD with suspected AMI and to calculate CKD- optimized diagnostic TnI thresholds.

Methods:
Of 1572 patients enrolled with suspected AMI, 266 patients showed an impaired renal function with estimated glomerular filtration rate (eGFR) of less then 60ml/min and were classified as patients with CKD. N=77 (34%) of patients with CKD and n=278 (24%) without CKD had the final diagnosis AMI. TnI was measured on admission and after 3h. Based on receiver operator characterics curve analyses (AUROC) of the baseline levels CKD optimized TnI threshold were derived. Sensitivity and specifity were calculated for the 99th percentile cut-off (30.0 pg/mL), the optimized cut-off (58.0 pg/mL) and the change in TnI concentration within 3h after admission.

Results:
Patients with CKD had higher TnI levels then patients without CKD (6.0pg/mL vs. 20.9pg/ml; p<0.001). This difference was more pronounced in patients without AMI (median 9.1 vs. 4.4; p<0.001), whereas the difference diminished in AMI patients (median 337.4 vs. 238.6; p=0.83).

In CKD patients TnI remained a strong marker to detect AMI with AUROC of 0.933 compared to 0.969 in patients without CKD.
Applying the 99th percentile threshold it was associated with a relevant loss of specificity in CKD patients with 80% compared to 96% in patients without CKD. This poor specificity could be regained by use of a higher CKD-optimized threshold or use of the change in TnI concentration within 3h leading to specificities of 90% and 96%, respectively.

Conclusions:
Patients presenting with suspected AMI and CKD have higher TnI levels on admission compared to patients without CKD leading to a low specificity detecting AMI in CKD patients. Using an CKD-optimized TnI cut-off level on admission or using the change in TnI concentration within 3h is able to regain this lost specificity.
Abstract 15384: Laminar Flow Regulates Endothelial Cell Metabolism via Long Non-coding RNA lncflow2
(Best of Basic Science Abstract)
Authors: Pfisterer Larissa , Hartung Teresa , Michalik Katharina M , Chen Wei , Zeiher Andreas M , Boon Reinier A , Dimmeler Stefanie 
Published: July 2021

Considering that the transcriptome consists largely of non-coding transcripts, we analysed the impact of atheroprotective laminar flow (20 dynes/cm2) on the expression of long non-coding RNAs (lncRNA) in human endothelial cells (EC) by RNA deep sequencing.
Among the significantly up-regulated lncRNAs, we specifically confirmed the up-regulation of lncflow2 upon laminar flow (3.4±1.5, p<0.05) and by overexpressing the flow-induced transcription factor KLF2 (1.95+0.2, p<0.05) by qRT-PCR. Lncflow2 is preferentially localized to the nucleus and RNA immunoprecipitation data indicate an association with the chromatin mark H3K27me3 suggesting that lncflow2 might epigenetically control gene expression.
Functionally, the reduction of lncflow2 using LNA-Gapmers suppressed spheroid sprout formation of ECs (34.7 % reduction, p<0.05) and increased expression of endothelial adhesion molecules suggesting that lncflow2 improves EC function and reduces endothelial inflammation. Furthermore, gene ontology analysis of exon microarray analysis with RNA of lncflow2-silenced ECs revealed a significant regulation of metabolic pathways, such as the mevalonate pathway, indicated by elevated acetyl-CoA-acetyltransferase-2, HMG-CoA-reductase and HMG-CoA-synthase-1 expression (confirmed by RT-PCR; all p<0.05). In this context, inhibition of the HMG-Co-reductase by atorvastatin rescued the diminished spheroid sprouting upon loss of lncflow2. To elucidate additional effects on endothelial metabolic function, a mass spectrometry metabolome screening revealed significant alterations in amino acid, glucose and lipid metabolism. Seahorse analysis confirmed these data showing an elevated respiration and fatty acid oxidation in lncflow2 silenced ECs.
Our data identify lncflow2 as a flow-regulated lncRNA that modifies EC metabolic responses by controlling metabolism-associated genes- particularly of the mevalonate pathway. Thereby, lncflow2 critically modifies EC functions and may play a regulating role in cellular metabolic adaption to stressors.
Abstract 16071: Electroanatomical Voltage and Morphology Characteristics in Post-infarction Patients Undergoing Ventricular Tachycardia Ablation
Authors: Tsiachris Dimitris , Silberbauer John , Oloriz Teresa , Mizuno Hiroya , Baratto Francesca , Della Bella Paolo , Stefanadis Christodoulos 
Published: July 2021

Introduction:
We analyzed the endo-epicardial electroanatomical mapping (EAM) characteristics, their association with clinical data and their prognostic value in a large cohort of post-myocardial infarction (MI) patients.

Methods:
We performed analysis of voltage (bipolar dense scar-DS and low voltage-LV areas, unipolar LV and penumbra areas) and morphology characteristics (presence of abnormal late-LPs and early potentials-EPs) in 100 post-MI patients undergoing EAM-based ventricular tachycardia (VT) ablation (26 endo-epicardial procedures). We defined as unipolar LV areas those with voltage <8 mV and unipolar penumbra area the unipolar LV area beyond the bipolar LV area. The ratio of bipolar DS to LV area reflected the fibrosis density within the infarct region.

Results:
Mean endocardial surface area was 236.1 cm2. Of that, 10.2% was bipolar DS, 21.8% was bipolar LV and 46.7% was unipolar LV. Endocardial penumbra was present in all but one patients and mean area was 51.6 cm2 (24.9%). There was no endocardial bipolar DS in 18% of the patients. Endocardial bipolar DS area >22.5 cm2 (sensitivity 61.1% and specificity 87.5%) best predicted scar transmurality.

Endocardial LPs were recorded in 66% of the patients and epicardially in 17/26 (65.4%). Endocardial bipolar DS area >7 cm2 (sensitivity 88.2% and specificity 66.7%) and endocardial bipolar scar density >0.35 (sensitivity 52.9% and specificity 100%) predicted epicardial LPs. Abolition of endocardial LPs was achieved in 51/66 (77.3%) and of epicardial LPs in 10/17 (58.8%) patients.
As a primary strategy, LPs and VT-mapping ablation occurred in 48%, only VT-mapping ablation in 27%, only LPs ablation in 17% and EPs ablation (in the absence of LPs) in 6%. After a median follow-up time of 628 days, endocardial LP abolition was associated (HR 0.274, p=0.01) with reduced VT recurrence (32%). Endocardial LP presence (HR 0.177, p=0.041) acted as a prophylactic predictor while increased endocardial penumbra area (HR=1.028, p=0.044) as an adverse predictor of cardiac death (7%).

Conclusions:
Endocardial scar extension and density predicted scar transmurality and endo-epicardial presence of LPs, although DS is not always identified in post-MI patients. LPs were abolished in 51% resulting in improved outcome.
Abstract 17136: MicroRNA-181b Inhibition Stabilises Abdominal Aortic Aneurysms by Promoting Collagen Accumulation and Elastin Deposition
Authors: Di Gregoli Karina , Mohamad Anuar Nur Najmi , George Sarah J , Johnson Jason L 
Published: July 2021

Increased matrix metalloproteinase (MMP) activity, and related collagen and elastin degradation as a result of macrophage accumulation, are key characteristics of abdominal aortic aneurysm (AAA) progression and rupture. Accordingly targeting MMPs or promoting expression of the endogenous tissue inhibitor of metalloproteinases (TIMPs), may represent novel therapeutic strategies to prevent AAA progression and rupture.
To closely mimic human AAA, we used an angiotensin II (AngII)-infused, high fat-fed apolipoprotein E knockout mouse model. Sudden death due to aortic dissection/rupture, was significantly increased (30%, p<0.001, n=20) in TIMP3 KO mice compared to wild-type controls, supporting a protective role for TIMP3 in AAA progression. Moreover Q-PCR revealed that microRNA (miR)-181b, a validated repressor of TIMP3 protein expression, was up-regulated 22-fold (n=6, p<0.001) in human AAA compared to non-aneurysmal sites. In vitro, miR181b inhibition increased macrophage TIMP3 protein expression 3-fold (n=4, p<0.05), highlighting miR181b inhibition as a potential approach to retard AAA progression. Indeed using a miR181b inhibitor, AAA development and inflammation was retarded in AngII-infused high fat-fed ApoE KO mice. This effect was characterised by a 56% reduction in macrophage content (n=5, p<0.05), augmented collagen content 1.9-fold (n=5, p<0.05) and collagen fibre thickness (+24%, p<0.05) in AAAs compared to scrambled-miR control animals. AAA elastin content was also increased (1.5-fold, n=5, p<0.05) in miR181b inhibitor treated mice versus controls. Collagen accumulation was TIMP-3 dependent as miR-181b inhibition did not affect collagen levels in TIMP-3 KO mice. However elastin content remained elevated in miR-181b inhibitor treated TIMP3 KO mice (2-fold, n=6, p=0.001), suggesting a TIMP-3 independent mechanism. In vitro miR181b inhibition in smooth muscle cells revealed a 2.5-fold increase in elastin production (n=3, p<0.05), supporting a direct role for miR-181b in elastin regulation.
Collectively our data show that miR181b inhibition stabilises AAA through a dual beneficial effect, by promoting collagen preservation via TIMP3 modulation, and through directly increasing elastin production and deposition.
Abstract 18266: Overactive Tgfβ Signaling in Smooth Muscle Cells Induces Hypertension in Mice Through Increased Myogenic Tone and is Responsible for Increased Myogenic Tone in Resistance Vessels of Hypertensive Patients
Authors: Carnevale Daniela , Casaburo Manuel , Bizzotto Dario , Cugino Daniela , Selvetella Giulio , Innocenzi Gualtiero , Bressan Giorgio , Lembo Giuseppe 
Published: July 2021

Emilin1 (E1) is a protein of the extracellular matrix that regulates TGFβ activity through proteolysis of the proTGFβ. E1 KO mice are hypertensive, with increased TGFβ activation. As E1 is expressed in blood vessels starting from embryonic life to adulthood, is still unknown whether the E1 KO phenotype results from a developmental defect or lack of a homeostatic role exerted in the adult. To dissect this issue, we inactivated E1 in smooth muscle cells (VSMCs) of adult mice, by the use of floxed E1 and CreERT2 [a tamoxifen (TAM) inducible Cre recombinase] under the control of the smooth muscle myosin heavy chain (Smmhc) promoter. When Smmhc-CreERT2 E1fl/fl mice were given TAM, blood pressure significantly increased (124±1 vs basal condition 106±1 mmHg) as well as myogenic response in resistance arteries (16.3±0.7 vs basal condition 11.4±0.1 % at 125 mmHg).
In order to evaluate the relevance of our findings in the human pathology, we enrolled 20 hypertensive and 20 normotensive patients that underwent neurosurgical intervention for primary lumbar hernia repair and dissected out resistance vessels from skeletal muscle biopsies. We analyzed the myogenic tone of human peripheral resistance vessels in a pressure myograph and randomized vessels to receive vehicle, a neutralizing antibody anti-TGFβ or a preimmune non relevant IgG. As first, we found that hypertensive patients had significantly increased myogenic tone as compared to normotensive (16.6±2.1% vs 10.5±0.4% at 125 mmHg). Moreover, the pretreatment of vessels with anti-TGFβ antibody normalized the myogenic tone of hypertensive patients (10.8±0.6%) to the levels of normotensives (11.8±1.3%). A pretreatment with the non relevant IgG did not modify the myogenic tone of hypertensives (17±0.6%), thus demonstrating that the effect was dependent of an increased TGFβ signaling in vessels of hypertensive patients.
Overall, our results suggest that the TGFβ pathway in VSMC, is crucial for the myogenic tone of resistance arteries and is linked to the regulation of blood pressure. The data obtained in peripheral resistance vessels from hypertensive patients, that display an increased myogenic tone dependent on overactive TGFβ signaling, highlight the translational potential of our findings to the human pathology.
Abstract 19433: Should Bilateral Internal Thoracic Artery Grafting be Used in Patients After Recent MI?
Authors: Loberman Dan , Mohr Rephael , Medleg Mohamad , Nesher Nachum , Aizer Zahi , Paz Yoseph , Pevni Dmitri , Ben Gal Yanai 
Published: July 2021

Introduction:
Bilateral internal thoracic artery(ITA) grafting is associated with improved survival. However, many surgeons are reluctant to use this revascularization technique in patients after myocardial infarction (MI) due to the risk of sternal infection and the excellent survival benefit obtained with single ITA (SITA).

Hypothesis:
Long-term outcome of bilateral ITA (BITA) grafting, might be superior to single ITA and other conduits such as saphenous veins (SVG) and radial artery (RA) in patients with multi-vessels disease after recent MI.

Methods:
871 patients who underwent BITA grafting after recent MI (<3 months prior to surgery), between 1996 and 2010, Were compared with 527 who underwent CABG with SITA and SVG or RA.

Results:
Patients undergoing SITA were older, more often female, more likely to have COPD, EF<30%, preoperative critical state, Diabetes, chronic renal failure (CRF), peripheral vascular disease (PVD) and emergency operation. In contrast, patients undergoing BITA grafting were more likely to have triple vessel disease and more often underwent CABG with three or more grafts and sequential grafts.

Operative mortality of BITA patients was lower (3.0 % vs. 5.7%, in the SITA group p=0.01), Occurrences of sternal wound infection (3% vs 2%) and strokes (2.6% vs. 3%) were similar. Mean follow-up was 11.8 (95%CI 10.95-12.56) years. Kaplan Meier survival of BITA patients was better (70.3% vs.52.6% p<0.001). Propensity score matching was used to account for differences between groups in preoperative characteristics. The 293 matched pairs thus created had similar preoperative characteristics.
Kaplan Meier 10 year survival (67.3% versus 59%, p=0.325 log-rank test), and the Cox adjusted survival of the matched groups did not reach statistical significance (HR 1.57, p=0.091). However, survival of non- emergent BITA patients was better (HR 1.256 p=0.038). Age, COPD, CHF, CRF, PVD and left main were independent predictors of decreased survival. Off-pump operations were associated with improved survival (Cox model)

Conclusions:
This study suggests that long-term outcome of arterial revascularization with BITA can be better than that of SITA in non-emergency cases after recent MI with proper patient selection
Abstract P031: Correlation of Sibling Lipid Levels From a Statewide Child Cardiac Risk Factor Registry
Authors: Pyles Lee A , Lilly Christa , Neal William A 
Published: July 2021

Introduction:
Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) is a project that has assessed childhood risk factors for cardiovascular disease (CVD) for nearly twenty years. We have screened approximately 95,000 children from WV that now include 60,403 with lipid panels. Eight-thousand-five-hundred-fifty-seven persons have one or more siblings who have participated in the project. To begin to consider genetic primordial antecedents of CVD in WV schoolchildren, we linked sibships for analysis.

Methods:
Linkage software designed to deduplicate EHRs proved poorly adaptable to the problem of family matching. Successive excel spreadsheets were used to directly match either mother or father’s first and last name with care taken to avoid similar names by requiring additional matching parameters. A group of children were identified with younger siblings subsequently enrolled in CARDIAC and the two older children were matched for analysis when 3 siblings were found. Body Mass Index z-score was calculated for each child. Fasting lipid levels were obtained by venipuncture and measured by a commercial laboratory (LabCorp).

Results:
Children (5259)with at least one sibling with LDL levels available for both were found along with 1384 third siblings. The mean LDL level for the first child was 90.5 mg/dl and 92.1 mg/dl for the second child. The mean BMI z-score was +0.83 for the group of 95,000 children, +0.73 for the first sibling and +0.72 for the second sibling. Sibling BMI z-scores were strongly correlated. Multivariate analysis demonstrated that the LDL level for the second child correlated strongly with both the older sibling’s LDL level and with the second child’s BMI z-score. This model showed R2 = 0.15 and the following prediction equation:

LDLsibling2 = 56.3 + 0.377*LDL-proband + 2.24*BMI-z-score-sibling2
p = 4.33 x 10 -175 for LDL and p = 4.06 x 10 -15 for BMI z-score
Six-hundred-sixty-eight children had an LDL level greater than 130 mg/dl including 88 sets of siblings. 12 pairs of siblings each had an LDL level > 160 mg/dl.

Conclusion:
the analysis demonstrates a strong correlation between sibling LDL-c levels that is not as well explained by the correlation of BMI z-score as by LDL-c. This analysis along with our recent study of LDL and height will help to characterize CVD risk in this population to focus future investigations in children and families.