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Gene expression profiling in Wistar male rat left ventricle with chronic and severe aortic valve regurgitation

ABSTRACT: Aortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV) which results in dilation, eccentric hypertrophy and eventually loss of function. Little is known about the impact of AR on LV gene expression. We therefore conducted a gene expression profiling study in the LV of male Wistar rats with chronic (9 months) and severe AR.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE17050 | GEO | 2010/03/31

SECONDARY ACCESSION(S): PRJNA117777

REPOSITORIES: GEO

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Gene expression profiling in Wistar male rat left ventricle with chronic and severe aortic valve regurgitation

Project description:Aortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV) which results in dilation, eccentric hypertrophy and eventually loss of function. Little is known about the impact of AR on LV gene expression. We therefore conducted a gene expression profiling study in the LV of male Wistar rats with chronic (9 months) and severe AR. Five male Wistar rats had one or two aortic valve leaflets punctured with a catheter under echocardiographic guidance in order to induce severe regurgitation (>65% of blood regurgitating during diastole from the aorta to the left ventricle). Five additional rats were sham-operated. The animals were sacrificed 9 months after the procedure and their left ventricle collected for RNA extraction and microarray analysis.

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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,

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