Project description:Dissecting abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Complex, complicated, and extremely heterogeneous diseases like dissecting AAAs severely limit our ability to understand it. A thorough understanding of cell types and signaling pathways associated with the initiation and progression of dissecting AAA is essential for the development of medical therapy. Single-cell RNA sequencing (scRNA-seq) was performed on the abdominal aortas from ApoE-/- mice at days 28 post-Angiotensin II-induced mouse dissecting AAAs. According to the Angiotensin II-induced dissecting AAA model described in this study, alterations in cellular subpopulations, fractions, and transcriptome profiles are present.
Project description:In this study we used microarrays to examine relative genes expression within the aorta of ApoE-/- infused with angiotensin II in relation to aneurysm formation. Infusion of angiotensin II induces aortic dilatation particularly of the suprarenal aorta in ApoE-/- mice. Based on studies carried out in our and other laboratories the response to angiotensin II is variable, with some mice developing large aneurysms but other animals appearing resistant to aneurysm formation with aortic diameters similar to that of saline controls. We compared RNA expression from whole aortas of 17 week old male ApoE-/- mice exposed to angiotensin II (1.44 µg/kg/min) for 4 weeks where there was clear evidence of aortic aneurysm formation (n=5) with that of mice failing to develop aneurysms (n=7) and those exposed to saline infusion (n=6). AAA was defined as diameter of suprarenal aorta greated than 1.5mm measured on photographs of aortas at necroscopy. Keywords: Disease state analysis 18 samples analysed, AAA (n=5), no AAA (n=7), saline (n=6). AAA - abdominal aortic aneurysm
Project description:Vascular smooth muscle cell (VSMC) phenotypic switching is widely recognized as a key mechanism responsible for the pathogenesis of several aortic diseases such as aortic aneurysm. Cellular communication network factor 2 (CCN2), often upregulated in human pathologies and animal disease models, exerts a myriad of context-dependent biological functions. However, current understanding of the role of SMC-CCN2 in SMC phenotypic switching and its function in the pathology of abdominal aortic aneurysm (AAA) is lacking. Here we report the effect of SMC-restricted CCN2 deficiency of hypercholesterolemic mice on gene expression in infrarenal aorta with or without angiotensin II (Ang II)-infusion.
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.
