bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 699: Mitochondrial Aldehyde Dehydrogenase (aldh-2) Protects Against Lipopolysaccharide-induced Myocardial Contractile Dysfunction by Suppression of ER Stress via Regulation of Autophagy
Authors: Pang Jiaojiao , Xu Xihui , Zhang Yingmei , Chen Yuguo , Ren Jun 
Published: March 2022

Lipopolysaccharide (LPS), a constituent of the outer membrane of Gram-negative bacteria, is the principal culprit factor responsible for the development of multi-organ failure including septic heart failure - a major contributor to increased mortality in patients with sepsis. However, there is still no efficacious treatment for septic cardiomyophathy. ALDH2 is well-known for its distinct beneficial role in cardiac pathologies including heart failure, ischemia and reperfusion injury. Little is known with regards to its effect on septic cardiomyopathy and the underlying mechanism. This study was designed to examine whether ALDH2 affects LPS-induced myocardial dysfunction and the underlying mechanism involved with a focus on ER stress and autophagy.
WT and ALDH2 transgenic mice were subjected to LPS (4 mg/kg, 4 h). Myocardial mechanical and intracellular Ca2+ properties were examined in FVB wild-type and ALDH2 transgenic mice using echocardiography and IonOptix SoftEdge techniques. Protein markers for ER stress, autophagy and related signaling molecules were evaluated. LPS compromised cardiac contractile function shown as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca2+ homeostasis, associated with overt ER stress, upregulated autophagy, suppressed phosphorylation of Akt and its downstream signal molecule mTOR, the effects of which were attenuated by ALDH2. In vitro study revealed that the ER stress inducer tunicamycin exacerbated LPS-induced myocardial dysfunction, which was abrogated by the ALDH2 activator Alda-1 and the autophagy inhibitor 3-MA. Interestingly, the beneficial effect of Alda-1 was obliterated by the autophagy inducer rapamycin, Akt inhibitor AktI and mTOR inhibitor RAD001.
We conclude that ALDH2 protects against LPS-induced myocardial dysfunction possibly through suppression of ER stress and inhibition of autophagy.
Abstract 8: RNA-binding Protein Quaking Maintains Endothelial Barrier Function Through β-catenin and VE-cadherin
Authors: de Bruin Ruben G , Dane Martijn J , Lee Dae Hyun , Roeten Marko K , Schmidt Iris , Bijkerk Roel , van der Veer Eric P , de Boer Hetty C , Rabelink Ton J , van Zonneveld Anton Jan , van Gils Janine M 
Published: March 2022

Endothelial barrier function plays a major role in the onset of atherosclerosis. This barrier is determined largely by adherens junctions. Remarkably little is known about their regulation at the post[[Unable to Display Character: &#8208;]]transcriptional level. We find that the RNA-binding protein Quaking (QKI), known for its function in embryonic blood vessel formation, is highly expressed in quiescent adult endothelial cells (EC) in vivo. In vitro, EC displayed increased levels of QKI when cultured under laminar atheroprotective flow. Using KLF2 overexpression and a human QKI promoter reporter gene, we found that KLF2 mediates this increase in QKI expression.
Subsequently we aimed to investigate the role of QKI in EC vascular integrity. Silencing of QKI markedly impaired (0.65 fold ±0.13; p<0.05) the capacity to form a high resistance endothelial monolayer, as measured using Electric cell-substrate impedance sensing. To confirm a role for QKI in maintaining EC barrier function in vivo, we measured Bradykinin-induced vascular leakage in QKI viable mice (QKIv), which express decreased levels of the QKI protein. Indeed, QKIv mice displayed a 20% (p<0.05) increase in extravascular accumulation of Evans blue-labeled albumin compared to wild type littermates. Interestingly, the mRNA of both β-catenin and VE-cadherin, the prime adhesion proteins in EC adherens junctions, contain conserved QKI-binding sites. Moreover the targeted reduction of QKI resulted in a reduction of β-catenin and VE-cadherin protein expression. Importantly, we identified a direct role for QKI in regulating mRNA biology of β-catenin and VE-cadherin, as RNA immunoprecipitation and luciferase-reporter assays revealed that QKI can directly bind to the mRNA and induces transcript translation, respectively. This effects was perturbed upon reduced QKI expression.
In conclusion, we show that QKI functions as a critical regulator of β-catenin and VE-cadherin in endothelial cells, and the modulation of QKI expression affects endothelial monolayer integrity, in vitro and in vivo. These studies provide novel insight into the importance of post-transcriptional regulation of components of the endothelial adherens junction, and may have wide ranging implications for the preservation of vascular integrity in disease.
Abstract 177: Follow-up Study of Thrombus in Coronary Aneurysms due to Kawasaki Disease.
Authors: Suzuki Atsuko 
Published: March 2022

The features of MR coronary angiography (MRCA) are able to detect arterial walls and thrombus in aneurysms clearly by using the sequences of black blood methods.
Up to now 262 patients have been followed up by MRCA(the average 3.5 times ±2.3 times), The duration of the follow up is 4.7years±3.3years, During the periods, the coronary arterial lesions have changed as follows; decreased size of aneurysms in 116 patients out of the 262 (44.3%), enlargement of aneurysm in 2 (0.8%), newly appeared or progressed degree of localized stenosis in 26 (9.9%), appearance of occlusion in 5 (1.9%), recanalized vessels in 20 (7.6%). These changes are related to thrombus formation, thrombolysis and thickening of arterial walls.
The thrombus often change their locations in the aneurysm, sizes, even disappear and some of them develop to recanalized vessels.
Thin membranes in aneurismal lumen and tiny polyps on the intima were often detected (Fig),These constructions and thrombus in aneurysms are observed to be still changeable even more than 2 decades after the onset of Kawasaki disease.
Therefore, MRCA is the most convenient for following up CAL frequently and noninvasively.
Abstract 213: Caracteristics of Kawasaki Disease in Chile: Temuco′s experience
Authors: Soza Guillermo , Cerda Carolina , Berkhoff Andreas , Lozano Claudia , Salgado Andrea 
Published: March 2022

Kawasaki Disease (KD) is a vasculitis mainly affecting children under two years old and harms arterial vessels (especially coronary) causing dilatation, aneurysms and eventual myocardial complications. Though etiology is unknown, a relationship with an infectious agent is suspected.
Diagnosis is doing by clinical criteria and laboratory support. KD cases reported in Latin America go along abscence of management protocols and it is not considered notifiable disease. In order to contribute to a greater understanding of this disease, a retrospective - descriptive analysis of 75 patients diagnosed with KD at the time of discharge was carried out from January 2005 to August 2014 at Hospital Dr.Hernán Henríquez Aravena, Temuco, Chile. Information was tabulated in Microsof Office Excel 2007 and a statical analysis were performed using STATA 11.0 program.
Average age 2 years 7 months (range 2 months to 17 years). Sex Male/Female 49%/51%. Prior consultations 85% (64/75). Initial diagnosis KD 51% (38/75). Fever 100% (75/75), 64%(48/75) about 39 ° C. Eye involvement 68% (51/75). Oropharyngeal erythema 87% (55/75). Strawberry tongue 40% (30/75). BCG erythema 19% (14/75). Rash 83% (62/75). Erythema/oedema of hands and foots 73% (55/75). Cervical adenopathy 41% (31/75). Irritability 55% (41/75). Leukocytosis 36% (27/75). Plaquetosis 69%(52/75) and periungual descamation 39% (29/75). Echocardiogram abnormal at startup 28% (21/75), (6/75)8% prior application of IVGG and 5%(4/75)remained with coronary involvement. A single dose of 2g/kg of Intravenous Gamma Globuline (IVGG) was administrated to 97%(73/75). Aspirin 50 mg/kg initial and 5 mg/kg during the following. A second dose of IVGG was required in 13% (10/75). Two patients were treated with anticoagulant for giant aneurysms and in one case, bilateral brachial aneurysms. Tipycal KD in 73% (55/75) and 27%(20/75) incomplete.
Further clinical suspicion is needed, because a high percentage of patients had coronary involvement at diagnosis. Those who received early IVGG coronary involvement were lower. Prominent among coronary involvement factors are extreme age, atypical or incomplete forms and high RCP. Needed be considered KD as a notifiable disease, considering the economic and social implications.
Abstract 80: Correlation of N-terminal pro-BNP Release with Myocardial Involvement in Acute Kawasaki Disease
Authors: Fournier Anne , Desjardins Laurent , Dahdah Nagib 
Published: March 2022

N-terminal pro-BNP (NT-proBNP) is elevated at the onset of Kawasaki Disease (KD). This is based on the hypothesis of immune myocardial inflammation. We sought to study the relationship between NT-proBNP and cardiac function in KD.
Parameters of myocardial involvement determined by ECG (PR and QTc intervals, QT dispersion, R-T axis) and by echocardiogram (systole and diastole) were correlated with levels of NT-proBNP in the acute (1 week), sub-acute (2-3 months) and chronic (6 months to 1 year) phases of KD. KD patients were compared to a febrile group. KD patients were further subdivided into 2 groups according to the levels of NT-proBNP; normal NT-proBNP (NT-proBNP Z-score < 2), or elevated NT-proBNP (Z-score ≥ 2).
There were 56 subjects (14 controls, 19 KD-1 and 23 KD-2 patients), with similar age at assessment (3.8±4.3 vs. 3.3±2.3 years-old, p=0.609). Myocardial contractility was significantly lower in KD patients in the acute phase with an ejection fraction of 57.4±7.5% compared to CTL 61.9±6.5%; p=0.049). Myocardial dysfunction was more significant in KD with high NT-proBNP compared to those with normal NT-proBNP, (shortening fraction Z-score of-1.6±1.5 versus -0.5±1.5; p=0.025) QTc interval was longer in KD compared to febrile CTL (412.3±21.0 mS vs. 390.6±14.6 mS, respectively; p=0.009). In contrast, there were no significant differences for left ventricular mass index (p=0.935) or LV end-diastolic diameter (p=0.565). Likewise, there were no significant differences for the PR interval (p=0.344), QT dispersion (p=0.288) or R-T axis (p=0.577). Otherwise, there was a significant correlation between coronary artery involvement (CA z-score ≥ 2.5) and the likelihood of lower LV ejection fraction (p=0.049) and higher NT-proBNP z-score (p=0.043), but no correlation with normalized LV shortening fraction (p=0.16) or QTc (p=0.14). The anomalous findings disappear in the sub-acute phase. On the other hand, a lengthening of QTc interval in the acute phase, irrespective of NT-proBNP status, resolves after 2-3 months.
In acute KD, there is a reduction in myocardial function, to a higher extent in cases with elevated NT-proBNP. This correlates with coronary artery involvement. KD patients with elevated NT-proBNP z-score may warrant careful follow-up.
Abstract O.14: Incidence rate of recurrent Kawasaki disease in Japan (2003-2012)
Authors: Sudo Daisuke , Nakamura Yosikazu 
Published: March 2022

To investigate the incidence of recurrent Kawasaki disease, data of nationwide surveys of Kawasaki disease in Japan from January 2003
(18th survey) to December 2012 (22th survey) are analyzed. Our group previously reported the incidence rate of recurrent Kawasaki disease (Nakamura et al., 1994 and Hirata et al., 2001). In the current study, 104,751 patients with 498,388.9 person-years are observed to calculate the rate of recurrence. The incidence rate of recurrence is 4.14 per 1,000 person-years, with a high incidence within the 12 months from the first episode. The observed person-year categorized by some variables is calculated, such as sex, age at first episode, period of time after the initial episode, presence of cardiac sequelae in the acute (within 2 months) and late (after 2 months) stage, exposure to intravenous gamma globulin (IVGG) therapy, presence of additional IVGG administration, and exposure to steroid therapy. Using those data, incidence rate of recurrent Kawasaki disease and incidence rate ratio are calculated according to such variables, and potential risk factors for recurrence of Kawasaki disease are discussed.
Abstract 17324: Associations Between Individual Saturated Fatty Acid Intake and Risk of Coronary Heart Disease Among American Men and Women
Authors: Zong Geng , Wanders Anne , Marjan Alssema , Zock Peter , Sun Qi 
Published: March 2022

Dietary intervention studies report neutral effects of stearic acid (18:0) on blood lipids, compared with lauric acid (12:0), myristic acid (14:0) and palmitic acid (16:0). Evidence from observational studies on the associations between intakes of individual saturated fatty acids (SFAs) and risk of CHD is scarce.
We prospectively followed 72,102 women in the Nurses’ Health Study (1984-2010) and 42,874 men in the Health Professionals Follow-Up Study (1986-2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by validated food-frequency questionnaire and updated every 4 years.
Baseline percentages of energy from total and major 4 subgroups (4:0-10:0, 12:0-14:0, 16:0, and 18:0) of even-chain SFA, were 11.8%, 0.6%, 1.3%, 6.6%, and 3.3% for women, and 10.8%, 0.5%, 1.1%, 6.1%, and 3.1% for men. Spearman correlations among baseline individual SFA intakes ranged from 0.43 (between 4:0-10:0 group and 18:0 in both cohorts) to 0.92 (between 16:0 and 18:0 in women). We generated 18:0 residual by regressing 18:0 on intakes of other SFAs. During 2.6 million person-years of follow-up, 6,843 incident CHD cases were documented. In the multivariate model, intakes of 4:0-10:0, 12:0-14:0, and 16:0, but not 18:0, were positively associated with risk of CHD (P<0.05). After further adjusting for dietary factors, hazard ratios (95% confidence interval, HR[95%CI]) of CHD per 1% energy increase were 1.10 (0.98, 1.22; P=0.10) for 4:0-10:0, 1.11 (1.03, 1.18; P=0.003) for 12:0-14:0, 1.09 (1.04, 1.13; P<0.001) for 16:0, and 0.98 (0.94, 1.01; P=0.22) for 18:0. The HR per 0.2 increase in the ratio of polyunsaturated fat (PUFA) to SFA was 0.93 (0.90, 0.96; P<0.001). The HRs of CHD risk per 1% of energy PUFA replacing SFA were 0.92(0.85,0.99; P=0.03) for 12:0-14:0 and 0.91(0.87,0.95;P<0.001) for 16:0; but PUFA replacing 4:0-10:0 or 18:0 were not associated with CHD risk: HRs were 0.98(0.86,1.11; P=0.74) and 0.97(0.93,1.01; P=0.19), respectively.
Our findings indicate that while 12:0-16:0 were associated with increased CHD risk, short-to-medium-chain SFA and 18:0 were not. However, our results need to be interpreted with caution because saturated fatty acids share common food sources and are highly correlated.
Abstract 18166: Increasing Endothelialization of BMS and DES With Intra-arterial AdVEGF-A Gene Therapy in Porcine Coronary Arteries
Authors: Hytonen Jarkko P , Halonen Paavo , Tarvainen Santeri , Taavitsainen Jouni , Kuivanen Antti , Koistinen Arto , Laakkonen Johanna , Hartikainen Juha , Yla-Herttuala Seppo 
Published: March 2022

We aimed to increase stent endothelialization with gene therapy known to promote endothelial proliferation. In addition, we evaluated OCT and angioscopy imaging as tools for detecting endothelium with comparison to robust ex-vivo analyses including scanning electron microscopy (SEM), multiphoton microscopy and immunohistology.
24 stents, BMS and DES, were implanted into naïve porcine coronary arteries and received either AdVEGF-A or control AdLacZ gene therapy with a porous drug delivery catheter. Stents were imaged in-vivo with angiography, OCT and angioscopy immediately after stenting and one week and two weeks after stenting and gene therapy. At d14 the stents were collected for histology, multi-photon microscopy and scanning electron microscopy for assessment of endothelialization. Strut coverage was analyzed from SEM images and graded 0 (no coverage) to 3 (fully covered). Angioscopy pullbacks were analyzed for thrombus in the stented artery and graded similarly 0 (no thrombus) to 3 (occlusive thrumbus).
Initial SEM analyses from stented arteries two weeks after intervention showed increased strut coverage with BMS after VEGF-A gene therapy compared to control LacZ (2.8±0.4 vs. 1.8±0.4, p=0.0031, respectively, a) and b) in figure). Gene therapy did not change strut coverage in DES with stent coverage of 1.6±0.5 and 1.8±0.4, p=NS, AdLacZ and AdVEGF-A respectively. Angioscopic thrombus formation was low in all groups with a trend towards less thrombi on BMS groups (0.2±0.4 and 0.3±0.5 in AdLacZ and AdVEGF-A) compared to DES (0.8±0.8 and 0.8±0.7 in AdLacZ and AdVEGF, c) in figure with red thrombus at 4 o'clock).
AdVEGF-A treatment at the time of stenting increased coverage of BMS but did not improve healing of DES two weeks after stenting. Likely the strong cytotoxic drugs in DES hamper stent healing even with local supraphysiological growth factor concentrations. Angioscopy may be useful in assessment of arterial healing after treatment with a coronary stent.
Abstract 18216: Essential Role of Platelet Glycoprotein Ibα Dependent Thrombin-FXI Feedback Loop in Arterial Hypertension, Vascular Dysfunction and Inflammation
Authors: Kossmann Sabine , Jäckel Sven , Jurk Kerstin , Ehlken Moritz , Lagrange Jérémy , Schönfelder Tanja , Knorr Maike , Brandt Moritz , Karbach Susanne H , Daiber Andreas , Oelze Matthias , Walter Ulrich , Renné Thomas , Ruf Wolfram , Münzel Thomas , Wenzel Philip 
Published: March 2022

Interactions of platelets, leukocytes and the vessel wall play pivotal roles in activating coagulation and precipitating thrombosis. High levels of angiotensin II (ATII) cause arterial hypertension by a complex inflammatory pathway requiring leukocyte recruitment and reactive oxygen species production within the vessel wall coupled to vascular dysfunction.
Here we report an upregulation of tissue factor, thrombin-dependent endothelial cell VCAM-1 expression and integrin α4- and platelet-dependent leukocyte adhesion to arterial conductance vessels by ATII in vivo (1mg/kg/d for 7d). ATII-induced vascular dysfunction and Ccl2, VCAM-1 and Ly6C mRNA expression were ameliorated by thrombin inhibition, platelet-depletion as well as in hIL-4R/Ibα mice missing the extracellular ligand binding domains of GPIbα. Blockade of TF during ATII administration also attenuated vascular dysfunction and reduced vascular oxidative stress. Platelet rich plasma (PRP) of ATII-treated mice showed an increased thrombin evoked endogenous thrombin potential (ETP), whereas PRP from mice with pharmacological inhibition of FXI production or of hIL-4R/Ibα mice failed to amplify ETP following chronic ATII exposure. These data show that a FXI-dependent thrombin generation feedback loop requires GPIbα on platelets and suggest that TF-initiated coagulation promotes additional thrombin formation on platelets to cause vascular inflammation.
The therapeutic potential of blocking FXI synthesis via antisense oligonucleotides was generalized by experiments with 5/6 nephrectomized (5/6 Nx) rats. 5/6 Nx rats showed after 4 wk of surgery an endothelial dysfunction, increased blood pressure, vascular inflammation and oxidative stress, as well as a elevated ETP compared to sham whereas pharmacological inhibition of FXI synthesis attenuated these effects.
Our results reveal a critical role of platelet GPIbα to promote localized thrombin amplification and supporting a FXI-thrombin feedback loop in ATII-induced vascular inflammation. By using a FXI targeted approach, we propose a novel therapeutic possibility to interrupt this heterotypic cellular coagulation-inflammatory circuit.
Abstract 18939: Micro RNA-93 Promotes Macrophage M2 Polarization in Experimenal Peripheral Arterial Disease
Authors: Ganta Vijay C , Kutateladze Anna , Annex Brian , Leitinger Norbert 
Published: March 2022

Macrophages (MØ) were well known to play vital roles in promoting blood flow by arteriogenic induction in experimental Peripheral Arterial Disease (PAD). MØs depending on the cytokine milieu, exist in M1 or M2 polarization states (two extremes of polarization continuum). While M1-MØs are pro-inflammatory and anti-angiogenic, M2-MØs are anti-inflammatory and pro-angiogenic. We have previously demonstrated that Micro RNA-93 (Mir93) promotes angiogenesis and perfusion recovery in experimental PAD. However, the downstream mechanisms that operate in Mir93 mediated perfusion recovery in ischemic leg are not yet clear. In our current study we investigated the role of Mir93 in MØ polarization in vitro and in animal models of hind limb ischemic (HLI). We hypothesized that “Mir93 induction in ischemic muscle promotes M2-MØ polarization that improves tissue repair, survival and neovascularization in PAD”
Mir93 mimic transfection in Raw264.7 (MØ cell line) significantly induced Arginase-1 (M1 marker) expression and decreased inducible Nitric oxide synthase (iNOS) (M2 marker) expression compared to negative mimic in qPCR analysis. Bone marrow derived macrophages (BMDM) from MCM7-KO (Mir93 deficient mice) express significantly higher levels of iNOS compared to littermates under hypoxia serum starvation. Monocytes isolated from the bone marrow of MCM7-KO ischemic legs express significantly higher levels of iNOS compared to littermates. Conditioned medium from Antagomir-93 treated Raw264.7 MØs and MCM7-KO BMDM significantly decreased HUVEC capillary like tube formation on matrigel compared to negative antagomir treated or littermates. Flow cytometry analysis showed that MCM7-KO mice had significantly higher levels of M1-MØs correlating with decreased capillary density compared to litter mate controls. P<0.05 considered significant
We conclude that Mir93 plays a crucial role in inducing MØ-M2 polarization. Increased Mir93 levels in ischemic hind limb promote M2-MØ polarization that helps in recovery of ischemic leg by tissue repair and neovascularization. Ongoing experiments are aimed to determine whether Mir93 deficient MØs can inhibit perfusion recovery in littermates and the downstream targets of Mir93 that regulate MØ polarization in HLI