ABSTRACT
Trabeculation and compaction of the embryonic myocardium are morphogenetic events crucial for the formation and function of the ventricular walls. Fkbp1a (FKBP12) is a ubiquitously expressed cis-trans peptidyl-prolyl isomerase. Fkbp1a-deficient mice develop ventricular hypertrabeculation and noncompaction. To determine the physiological function of Fkbp1a in regulating the intercellular and intracellular signaling pathways involved in ventricular trabeculation and compaction, we generated a series of Fkbp1a conditional knockouts. Surprisingly, cardiomyocyte-restricted ablation of Fkbp1a did not give rise to the ventricular developmental defect, whereas endothelial cell-restricted ablation of Fkbp1a recapitulated the ventricular hypertrabeculation and noncompaction observed in Fkbp1a systemically deficient mice, suggesting an important contribution of Fkbp1a within the developing endocardia in regulating the morphogenesis of ventricular trabeculation and compaction. Further analysis demonstrated that Fkbp1a is a novel negative modulator of activated Notch1. Activated Notch1 (N1ICD) was significantly upregulated in Fkbp1a-ablated endothelial cells in vivo and in vitro. Overexpression of Fkbp1a significantly reduced the stability of N1ICD and direct inhibition of Notch signaling significantly reduced hypertrabeculation in Fkbp1a-deficient mice. Our findings suggest that Fkbp1a-mediated regulation of Notch1 plays an important role in intercellular communication between endocardium and myocardium, which is crucial in controlling the formation of the ventricular walls.
Subject(s)
Endocardium/metabolism , Heart Ventricles/pathology , Myocardium/metabolism , Receptor, Notch1/metabolism , Tacrolimus Binding Proteins/metabolism , Animals , Cell Lineage , Cells, Cultured , Embryo, Mammalian/embryology , Embryo, Mammalian/metabolism , Embryo, Mammalian/pathology , Embryonic Development , Endocardium/embryology , Endocardium/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Gene Expression Regulation, Developmental , HEK293 Cells , Heart Ventricles/embryology , Heart Ventricles/metabolism , Humans , Immunohistochemistry , Male , Mice , Mice, Knockout/embryology , Mice, Knockout/metabolism , Myocardium/pathology , Neural Crest/metabolism , Neural Crest/pathology , Phenotype , Receptor, Notch1/genetics , Signal Transduction , Tacrolimus Binding Proteins/genetics , TransfectionABSTRACT
Wet age-related macular degeneration (AMD) is the leading cause of visual impairment and vision loss in the elderly, and optical coherence tomography (OCT) enables revolving biotissue three-dimensional micro-structure widely used to diagnose and monitor wet AMD lesions. Many wet AMD segmentation methods based on deep learning have achieved good results, but these segmentation results are two-dimensional, and cannot take full advantage of OCT's three-dimensional (3D) imaging characteristics. Here we propose a novel deep-learning network characterizing multi-scale and cross-channel feature extraction and channel attention to obtain high-accuracy 3D segmentation results of wet AMD lesions and show the 3D specific morphology, a task unattainable with traditional two-dimensional segmentation. This probably helps to understand the ophthalmologic disease and provides great convenience for the clinical diagnosis and treatment of wet AMD.
ABSTRACT
To evaluate the distribution of choroidal thickness (CT) and its trend with age in healthy people using 120° ultra-wide field swept-source optical coherence tomography angiography (UWF SS-OCTA). In this cross-sectional observational study, healthy volunteers underwent single imaging of the fundus with UWF SS-OCTA at a field of view (FOV) of 120° (24 mm × 20 mm) centered on the macula. The characteristics of CT distribution in different regions and its changes with age were analyzed. A total of 128 volunteers with a mean age of 34.9 ± 20.1 years and 210 eyes were enrolled in the study. The thickest mean choroid thickness (MCT) was located at the macular region and supratemporal region, followed by the nasal side of the optic disc, and thinnest below the optic disc. The maximum MCT was: 213.40 ± 36.65 µm for the group aged 20-29, and the minimum MCT was: 162.11 ± 31.96 µm for the group aged ≥ 60. After the age of 50, MCT was significantly and negatively correlated decreased with age (r = - 0.358, p = 0.002), and the MCT in the macular region decreased more remarkably compared to other regions. The 120° UWF SS-OCTA can observe the distribution of choroidal thickness in the range of 24 mm × 20 mm and its variation with age. It was revealed that MCT decreased more rapidly in the macular region relative to other regions after 50 years old.
Subject(s)
Macula Lutea , Tomography, Optical Coherence , Humans , Adolescent , Young Adult , Adult , Middle Aged , Tomography, Optical Coherence/methods , Cross-Sectional Studies , Angiography , Choroid/diagnostic imaging , Macula Lutea/diagnostic imaging , Fluorescein Angiography/methodsABSTRACT
Primary cardiac tumors are extremely uncommon in young children and infants. Cardiac myxoma are typically found in the atria, predominately in the left atrium, with relatively few found on the right side, such as in the right ventricle or pulmonary artery. Numerous significant complications, including sudden death, can result from obstruction of the main pulmonary artery trunk and right ventricular outflow tract. Here, we describe the case of a 14-year-old Chinese girl diagnosed with a right ventricular myxoma located in the right ventricle and extended into the main pulmonary trunk. Complete resection of the myxoma and histological confirmation were performed.
ABSTRACT
Background: Right heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets. Methods: Monocrotaline was used to create an animal model of PH, and lung tissue was removed for transcriptome sequencing. The targets with the highest differences were chosen for transfection after possible targets were identified using bioinformatic techniques and confirmed by qPCR to examine their function in hypoxic PASMCs. Results: After sequencing 781 differentially expressed mRNAs, we compared them with the GEO dataset and found 43 differentially expressed genes. We chose the top three scores for further study and verification and discovered that MKI67, a crucial element of the cell cycle that regulates PASMC proliferation, had the greatest effect. After suppressing MKI67 in PASMCs, both cell proliferation and migration decreased. Conclusion: Several potential targets were chosen for this study, and MKI67 was found to play a regulatory role in cell migration and proliferation. This implies that PH can be diagnosed and treated using MKI67.