Publications by authors named "T J Ord"
Epigenetic therapy has gained interest in treating cardiovascular diseases, but preclinical studies often encounter challenges with cell-type-specific effects or batch-to-batch variation, which have limited identification of novel drug candidates targeting angiogenesis. To address these limitations and improve the reproducibility of epigenetic drug screening, we redesigned a 3D in vitro fibrin bead assay to utilize immortalized human aortic endothelial cells (TeloHAECs) and screened a focused compound library with 105 agents. Compared to the established model using primary human umbilical vein endothelial cells, TeloHAECs needed a higher-density fibrin gel for optimal sprouting, successfully forming sprouts under both normoxic and hypoxic cell culture conditions.
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- Abdominal obesity is linked to an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD).
- The study employed advanced genetic analysis methods, including RNA sequencing and Mendelian randomization, to explore how specific genes related to abdominal obesity impact MASLD at the cellular level.
- The research identified 17 key genes that mediate the effects of abdominal obesity on MASLD, demonstrating significant changes in adipocyte functions and highlighting the importance of these genes in the disease's development.
Cardiovascular disease plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics the gene expression changes in the human ex vivo right atrial tissue and pericardial fluid in ischemic heart disease, myocardial infarction, and ischemic and non-ischemic heart failure using asymptomatic patients with valvular disease who undergo preventive surgery as the control group. We reveal substantial differences in disease-associated gene expression in all cell types, collectively suggesting inflammatory microvascular dysfunction and changes in the right atrial tissue composition as the valvular and vascular diseases progress into heart failure.
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- The study investigates the gene expression changes in vascular cells during atherosclerosis progression, emphasizing the limited understanding of their clinical significance.
- It utilizes single-cell RNA sequencing data from both mouse models and human tissue to identify various cell subtypes involved in advanced atherosclerosis and symptomatic carotid plaques.
- The findings highlight the association of specific gene-regulatory networks with coronary artery disease severity, suggesting pathways that may be targeted for therapeutic strategies.
Background: CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of expression in endothelial cells.
Methods: To functionally characterize the coronary artery disease single-nucleotide polymorphisms harbored around the gene , we applied an integrative approach encompassing statistical, transcriptional (RNA-seq), and epigenetic (ATAC-seq [transposase-accessible chromatin with sequencing], chromatin immunoprecipitation assay-quantitative polymerase chain reaction, and electromobility shift assay) analyses, alongside luciferase reporter assays, and targeted gene and enhancer perturbations (siRNA and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) in human aortic endothelial cells.