Project description:Elastin wild type Eln+/+ and Eln+/- mouse aorta and aortic valve tissue. In the study, we demonstrated differential gene expression in juvenile elastin deficient mouse valve tissue. In the study, we hybridized RNA from Elastin wild type (Eln+/+) aorta tissue, elastin wild type (Eln+/+) aortic valve tissue, elastin (Eln+/-) aorta tissue and elastin (Eln+/-) aortic valve tissue to Affymetrix GeneChip Mouse Genome 430 2.0 Array
Project description:Elastin wild type Eln+/+ and Eln+/- mouse aorta and aortic valve tissue. In the study, we demonstrated differential gene expression in juvenile elastin deficient mouse valve tissue.
Project description:Genome wide DNA methylation profiling of ascending aorta tissue samples from normal, aortic dissection and bicuspid aortic valve patients with aortic dilation. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across more than 450,000 CpGs in ascending aorta samples. Samples included 6 normal donors, 12 patients with aortic dissection and 6 patients with bicuspid aortic valve and dilated aorta.
Project description:Bicuspid aortic valve is well known as a risk factor of dilation of ascending aorta. But the mechanisms of dialation are unknown. Morever, patients with bicuspid aortic valve tend to be aortic valve disease at younger age. After aortic valve surgery, if ascending aorta is dilated, the patient must be performed re-operation. For that reason, surgery for aortic root or ascending aorta is recommended to patient with bicuspid aortic valve with dilated ascending aorta. We thought that abnormality of cell cycle of the structure protein participated in ascending aorta dilation of patient with bicuspid aortic valve. We resected the wall of the ascending aota from patient undergoing aortic valve replacement for aortic valve stenosis during operation, and performed immunohistochemical staining for akt. Anti Akt antibodys were stained much on aortic media with bicuspoed aortic valve. Akt is a protein that is involved in mTOR / PI3K, and modulate the cell differenciation and proliferation. Further, the same samples were analyzed using a microarray method. On bicuspid aortic valve patients, the expression of TSC2 is reduced, and GβL is increased. TSC2 inhibit this pathway, and MLST8 activate this pathway. In the ascending aorta of BAV patients, PI3K / mTOR system is considered to be activated. When this pathway is activated, cell proliferation and cytodifferentiation are promoted abnormally,
Project description:This is an investigation of whole genome gene expression level in tissues of mice stimulated by LPS, FK565 or LPS + FK565 in vivo and ex vivo. We show that parenteral administration of a pure synthetic Nod1 ligand, FK565, induces site-specific vascular inflammation in mice, which is prominent in aortic root including aortic valves, slight in aorta and absent in other arteries. The degree of respective vascular inflammation is associated with persistent high expression of proinflammatory chemokine/cytokine genes in each tissue in vivo by microarray analysis, and not with Nod1 expression levels. The ex vivo production of proinflammatory chemokine/cytokine by Nod1 ligand is higher in aortic root than in other arteries from normal murine vascular tissues, and also higher in human coronary artery endothelial cells (HCAEC) than in human pulmonary artery endothelial cells (HPAEC), suggesting that site-specific vascular inflammation is at least in part ascribed to an intrinsic nature of the vascular tissue/cell itself.
Project description:This is an investigation of whole genome gene expression level in tissues of mice stimulated by LPS, FK565 or LPS + FK565 in vivo and ex vivo. We show that parenteral administration of a pure synthetic Nod1 ligand, FK565, induces site-specific vascular inflammation in mice, which is prominent in aortic root including aortic valves, slight in aorta and absent in other arteries. The degree of respective vascular inflammation is associated with persistent high expression of proinflammatory chemokine/cytokine genes in each tissue in vivo by microarray analysis, and not with Nod1 expression levels. The ex vivo production of proinflammatory chemokine/cytokine by Nod1 ligand is higher in aortic root than in other arteries from normal murine vascular tissues, and also higher in human coronary artery endothelial cells (HCAEC) than in human pulmonary artery endothelial cells (HPAEC), suggesting that site-specific vascular inflammation is at least in part ascribed to an intrinsic nature of the vascular tissue/cell itself. A fourty chip study using total RNA recovered from four isolated tissues of mice which were stimulated by various reagents. Aortic root, pulmonary artery, aorta and spleen of mice in 3 groups: 1) intraperitoneal injection of 20M-NM-<g of LPS priming only, 2) oral administration of FK565 (100M-NM-<g) for consecutive days, 3) oral administration of FK565 (100M-NM-<g) for consecutive days 1 day after LPS priming, at day 2, 4, and 7. And six chip study using total RNA recovered from three isolated vascular tissues of mice which were stimulated by FK565 (10M-NM-<g/mL) ex vivo.
Project description:BACKGROUND: The vast majority of thoracic aortic aneurysms (TAAs) are observed either together with a bicuspid aortic valve (BAV), a common congenital disorder, or in idiopathic cases such as patients with a normal tricuspid aortic valve (TAV). The main objective of our study was to identify shared and unique gene expression properties underlying the aortic dilation of BAV and TAV patients. METHODS AND RESULTS: Tissue biopsies for RNA and histological analyses were obtained from aorta of non-dilated (<40mm) and dilated (>45mm) aorta of BAV and TAV patients (in total 131 patients). Additional controls were from mammary artery of the same patients (n=88) and aorta from transplant donors (n=13). Gene expression profiles generated using Affymetrix Exon arrays were analyzed from controls and from aorta intima-media and adventitia of patients (in total 345 samples). 606 genes in aortic intima-media were found to be differentially expressed with dilation. Of these, only few (<4%) were differentially expressed in both BAV and TAV patients. Gene set enrichment analysis identified cell adhesion and extracellular region gene ontology sets as common features of TAA in BAV and TAV patients. The set of immune response genes was observed to be particularly overexpressed in aortic media of dilated TAV samples. CONCLUSION: The divergent gene expression profiles indicate fundamental differences in TAA etiology of BAV and TAV patients. Immune response activation solely in the aorta media of TAV patients suggests that inflammation is a causal factor of TAA in this patient group. Biobank of patient material. Each tissue sample is from a different patient as indicated by patient ID.
Project description:BACKGROUND: The vast majority of thoracic aortic aneurysms (TAAs) are observed either together with a bicuspid aortic valve (BAV), a common congenital disorder, or in idiopathic cases such as patients with a normal tricuspid aortic valve (TAV). The main objective of our study was to identify shared and unique gene expression properties underlying the aortic dilation of BAV and TAV patients. METHODS AND RESULTS: Tissue biopsies for RNA and histological analyses were obtained from aorta of non-dilated (<40mm) and dilated (>45mm) aorta of BAV and TAV patients (in total 131 patients). Additional controls were from mammary artery of the same patients (n=88) and aorta from transplant donors (n=13). Gene expression profiles generated using Affymetrix Exon arrays were analyzed from controls and from aorta intima-media and adventitia of patients (in total 345 samples). 606 genes in aortic intima-media were found to be differentially expressed with dilation. Of these, only few (<4%) were differentially expressed in both BAV and TAV patients. Gene set enrichment analysis identified cell adhesion and extracellular region gene ontology sets as common features of TAA in BAV and TAV patients. The set of immune response genes was observed to be particularly overexpressed in aortic media of dilated TAV samples. CONCLUSION: The divergent gene expression profiles indicate fundamental differences in TAA etiology of BAV and TAV patients. Immune response activation solely in the aorta media of TAV patients suggests that inflammation is a causal factor of TAA in this patient group.
Project description:Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA. Experiment Overall Design: Aneurysmal tissue of ascending aorta was collected from 13 patients with bicuspid aortic valve (BAV) and 12 patients with tricuspid aortic valve (TAV). Patients were selected on the basis of aortic diameter, age and other disease conditions. Patients with giant cell aortitis, cardiovascular abnormalities, inherited connective tissue disorders such as Marfan and Ehlers-Danlos syndrome were excluded from the study. RNA was extracted using Invitrogen RNA extraction kit and shown to be of adequate quality before application to Affymetrix microarray U133A gene chips probing for over 16,000 genes per chip. Two different methods of data analysis were performed: a linear model and GeneSpring.
Project description:Extracellular elastic fibres apply structure and mechanical elasticity to organs such as large arteries, lungs and skin 1. Elastic fibres are assembled through polymerization of tropoelastin monomers and loss of elastin is associated with aneurysmal degeneration of the aorta 2. The Fibulins are a six-member protein family hypothesized to function as intermolecular bridges that stabilize the organization of extracellular matrix structures such as elastic fibres and basement membranes 3. Fibulin-4 is found in the medial layers of arteries and moderately expressed in heart valves 4. To examine a potential role of Fibulin-4 in elastic fibre assembly and cardio-vascular disease we generated a mouse model underexpressing Fibulin-4. To get insight into the underlying molecular pathways involved in aneurysm formation, we determined the aorta transcriptome of Fibulin-4R/R animals and identified biological processes that were significantly overrepresented including apoptosis and cell death as well as several novel gene targets implicated in the response to aortic failure. We conclude that decreased Fibulin-4 expression causes aberrant composition of the elastin layers in the aorta and valvular leaflets, resulting in aortic aneurysms and heart abnormalities.