Gene Expression Profiles in Patients With Permanent Atrial Fibrillation (AF) Versus Sinus Rhythm (SR)
Recruitment status was: Recruiting
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Comparative Gene Expression Profiles in Patients With Permanent Atrial Fibrillation and Normal Sinus Rhythm|
- Expression profiles of genes related to apoptosis [ Time Frame: 6 months ]
- Expression profiles of pro-apoptotic and anti-apoptotic proteins [ Time Frame: 6 months ]
Biospecimen Retention: Samples With DNA
|Study Start Date:||December 2008|
|Estimated Study Completion Date:||December 2011|
Patients with degenerative mitral valve regurgitation and permanent atrial fibrillation who require mitral valve repair or replacement.
Patients with degenerative mitral valve regurgitation and maintaining sinus rhythm who require mitral valve repair or replacement.
Mitral valve regurgitation (MR) is the second most common valvular heart disease encountered in adults. Furthermore, atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice. Overall, 70% of the patients with severe MR are associated with AF independent from etiopathogenesis of MR. AF is clinically divided into three subgroups; 1) paroxysmal AF, occurs as episodes and ends spontaneously, 2) persistent AF, episodes terminate only with medical or electrical cardioversion, and 3) permanent AF, current medical treatments and electrical cardioversion does not restore a normal sinus rhythm. Despite intensive electrophysiological studies, the molecular mechanisms and pathways of AF are still not fully elucidated.
Apoptosis which has distinctive morphological and biochemical characteristics is genetically regulated, active programmed cell death process. It is known that cardiac morphogenesis restore from apoptosis. In addition, apoptosis has an important role in several cardiovascular system pathologies. It has been shown that atrial apoptosis causes numerous arrhythmias including AF. Likewise, in the pilot study which has been performed by our study group, AF is associated with apoptosis by immunohistochemical and DNA fragmentation analysis methods.
The aim of this project is to determine the morphological criteria of apoptosis in atrial tissues of patients with AF by using electron microscopy and immunohistochemistry. Moreover, we will investigate the transcriptional profile of AF associated genes by oligonucleotide microarray method. The gene expression profiles of patients with AF and degenerative MR will be compared with the atrial tissue samples from the patients with degenerative MR who preserve normal sinus rhythm which will serve as controls. In summary the apoptotic pathways would be analyzed at transcriptomic and genomic level. Besides, the pathways that may interfere AF pathophysiology would also be evaluated. The expression profiles of the genes primarily verified by quantitative real time RT-PCR will be further confirmed by translation of end-result proteins determined with Western blot technique. Thus, brand-new clues about physiology of fibrillating atrial cells would be achieved.
Keywords: Atrial fibrillation, apoptosis, oligonucleotide microarray
Please refer to this study by its ClinicalTrials.gov identifier: NCT00970034
|Ankara University Medical Faculty, Department of Cardiovascular Surgery,|
|Ankara, Turkey, 06340|
|Principal Investigator:||RUCHAN A AKAR, Assoc. Prof.||Ankara University|