Project description:Single-cell RNAseq (10x Genomics) analysis of the abdominal aorta in a murine model of Kawasaki Disease vasculitis (Lactobacillus casei cell wall extract, LCWE) and in control PBS-injected mice
Project description:Analysis of abdominal aorta gene expression in the LCWE-induced Kawasaki Disease vasculitis model and responisveness to Anakinra treatment in male and female 5 wk. old mice
Project description:Abdominal aortic aneurysm (AAA) is a permanent segmental dilatation of the abdominal aorta, contributing to a high mortality once rupture. We performed RNA-sequencing analysis of abdominal aorta tissues from 14 participants, including seven patients with AAA and seven control individuals.
Project description:Global gene expression information that can be used to identify pathways involved in the pathophysiology of disease. We used microarrays to identify which genes are expressed in either the abdominal aorta (control) or in abdominal aortic aneurysms (case), and also which genes may be differential between the two tissue states. Keywords: Characterization of expression in both diseased and non-diseased abdominal aortas.
Project description:Aortic aneurysms is increasing as the human population ages. Pathological oxidative stress is implicated in development of aortic aneurysms. We pursued a chemogenetic approach to create an animal model of aortic aneurysm formation using a transgenic mouse line DAAO-TGTie2 that expresses yeast D-amino acid oxidase (DAAO) under control of the endothelial Tie2 promoter. In DAAO-TGTie2 mice, DAAO generates the reactive oxygen species hydrogen peroxide (H2O2) in endothelial cells only when provided with D-amino acids. When DAAO-TGTie2 mice are chronically fed D-alanine, the animals become hypertensive and develop abdominal but not thoracic aortic aneurysms. Generation of H2O2 in the endothelium leads to oxidative stress throughout the vascular wall. Proteomic analyses indicate that the oxidant-modulated protein kinase JNK1 is dephosphorylated by the phophoprotein phosphatase DUSP3 in abdominal but not thoracic aorta, causing activation of KLF4-dependent transcriptional pathways that trigger phenotypic switching and aneurysm formation. Pharmacological DUSP3 inhibition completely blocks aneurysm formation caused by chemogenetic oxidative stress. These studies establish that regional differences in oxidant-modulated signaling pathways lead to differential disease progression in discrete vascular beds, and identify DUSP3 as a potential pharmacological target for the treatment of aortic aneurysms.
Project description:The ApoE -/- mice model of abdominal aortic aneurysm (AAA) involves introducing Angiotensin II subcutaneously to 14 week old male mice for 4 weeks by osmotic pump. A significant number of mice will develop aneurysm-like dilations in the suprarenal section of the abdominal aorta (SRA) that have a number of similarities to the human condition and make this a useful model of AAA. The mouse infrarenal aorta is very resistant to aneurysm formation while in humans AAA predominately occurs in the infrarenal section of the aorta (IRA). There have been a number of theories proposed to explain the site selctivity of aneurysm formation in AAA and this mice model. This study was designed to ascertain differences between SRA and IRA that may explain this site selectivity. Keywords: tissue type comparison
Project description:Vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (KCASP1Tg). GeneChip were performed to measure the changes in mRNA levels in the abdominal aorta.
Project description:Lysyl hydroxylase 1 (LH1) plays an important role in hydroxylation of lysyl residuel in Xaa-Lys-Gly. The hydroxylysine residues serve as sites of attachment for carbohydrate units which are essential for the formation of intra- and intermolecular collagen crosslinks. To gain mechanistic insights into the effects of LH1 deficiency on abdominal aortic aneurysm (AAA) formation, a whole transcriptomic analysis of abdominal aorta were performed using RNA-seq. The abdominal aorta of mice for RNA-seq were acquired at day 14 after angiotensin II infusion in order to provide the mechanistic or causal evidence of a direct participatory role of LH1 to the effects of AAA.
Project description:Spatial transcriptomics (Visium, Spatial 3' V1, 10x Genomics) analysis of heart tissues in a murine model of Kawasaki disease vasculitis