This study tested the hypothesis that Jagged2/Notches promoted the endothelial-mesenchymal transition (endMT)-mediated pulmonary arterial hypertension (PAH) (i.e. induction by monocrotaline [MCT]/63 mg/kg/subcutaneous injection) through increasing the expression of GATA-binding factors which were inhibited by propylthiouracil (PTU) (i.e. 0.1% in water for daily drinking since Day 5 after PAH induction) in rodent. As compared with the control (i.e. HUVECs), the protein expressions of GATAs (3/4/6) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly reduced, whereas the endothelial-phenotype markers (CD31/E-cadherin) were significantly increased in silenced JAG2 gene or in silenced GATA3 gene of HUVECs (all p < 0.001). As compared with the control, the protein expressions of intercellular signallings (GATAs [3/4/6], Jagged1/2, notch1/2 and Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly upregulated in TGF-ß/monocrotaline-treated HUVECs that were significantly reversed by PTU treatment (all p < 0.001). By Day 42, the results of animal study demonstrated that the right-ventricular systolic-blood-pressure (RVSBP), RV weight (RVW) and lung injury/fibrotic scores were significantly increased in MCT group than sham-control (SC) that were reversed in MCT + PTU groups, whereas arterial oxygen saturation (%) and vasorelaxation/nitric oxide production of PA exhibited an opposite pattern of RVW among the groups (all p < 0.0001). The protein expressions of hypertrophic (ß-MHC)/pressure-overload (BNP)/oxidative-stress (NOX-1/NOX-2) biomarkers in RV and the protein expressions of intercellular signalling (GATAs3/4/6, Jagged1/2, notch1/2) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/TGF-ß/α-SMA/p-Smad2) in lung parenchyma displayed an identical pattern of RVW among the groups (all p < 0.0001). Jagged-Notch-GATAs signalling, endMT markers and RVSBP that were increased in PAH were suppressed by PTU.
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http://dx.doi.org/10.1111/jcmm.17723 | DOI Listing |
Introduction Parenteral heparin is widely used as bridging therapy while optimising oral anticoagulation(OAC). Newer Direct-Acting OACs(DOACs) attain therapeutic effect very quickly. We report the use of dabigatran as bridging therapy during warfarin optimization for cardioembolic stroke in two patients who opted to receive warfarin for long-term anticoagulation for secondary stroke prevention.
View Article and Find Full Text PDFMed Image Anal
December 2024
Division of Pediatric Cardiology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address:
Patients with congenitally corrected transposition of the great arteries (ccTGA) can be treated with a double switch operation (DSO) to restore the normal anatomical connection of the left ventricle (LV) to the systemic circulation and the right ventricle (RV) to the pulmonary circulation. The subpulmonary LV progressively deconditions over time due to its connection to the low pressure pulmonary circulation and needs to be retrained using a surgical pulmonary artery band (PAB) for 6-12 months prior to the DSO. The subsequent clinical follow-up, consisting of invasive cardiac pressure and non-invasive imaging data, evaluates LV preparedness for the DSO.
View Article and Find Full Text PDFCardiol Young
December 2024
Pediatric Cardiology Unit, University of Padua, Padova, Italy.
Almost 20% of children with simple or complex types of CHD have a duct-dependent circulation The systemic-to-pulmonary shunt can be performed surgically, e.g., Blalock-Taussing shunt or with a patent duct arteriosus stenting.
View Article and Find Full Text PDFMagn Reson Med Sci
December 2024
Department of Radiology, Tianjin Chest Hospital, Tianjin, China.
Purpose: To investigate the potential of 4D flow MRI-derived pulmonary hemodynamic parameters as sensitive markers for chronic obstructive pulmonary disease (COPD) patients with right ventricular dysfunction (RVD).
Methods: We enrolled 15 COPD patients combined with RVD and 43 non-RVD participants, all of them underwent pulmonary function tests, thoracic CT and cardiac MR examinations, and the image post-processing analysis was completed. After comparing the 2 groups, the average flow velocity of the main pulmonary artery (Vavg-MPA) and the right pulmonary artery (Vavg-RPA) were identified as statistically significant confounding factors, propensity score matching was used to pair patients controlling for these 2 parameters.
Cell Rep
December 2024
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiology Division, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:
We sought to characterize cellular composition across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We performed single-nucleus RNA sequencing (snRNA-seq) in 78 samples in 10 distinct regions, including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins, which produced 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, with different cellular composition across cardiac regions and tissue-specific transcription for each cell type.
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