High-resolution two-dimensional gel electrophoresis analysis of atrial tissue proteome reveals down-regulation of fibulin-1 in atrial fibrillation.
BACKGROUND
Atrial fibrillation (AF) is the most common cardiac arrhythmia found in clinical practice. We combined high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) to compare the atrial proteome of subjects with AF versus controls with sinus rhythm (SR). Our aim was to identify novel differentially regulated proteins that could be related to the development of the arrhythmia.


METHODS
Human atrial appendage tissue samples from patients undergoing heart surgery with AF or SR were analyzed by high-resolution 2-DE. Proteins of interest were identified by MS and validated by western blotting and inmunohistochemistry.


RESULTS
Our analysis allowed the detection of over 2300 protein spots per gel. Following differential image analysis, we found 22 spot differences between the AF and SR groups in the 4-7 isoelectric point range, leading to the identification of 15 differentially regulated proteins. The main group of proteins identified was that of heat shock proteins (HSPs), including TRAP-1, HspB3, HspΒ6 and AHA1. Some of the differences detected between AF and SR for the above proteins were due to post-translational modifications. In addition, we identified the structural protein fibulin-1 as down-regulated in atrial tissue from AF patients.


CONCLUSIONS
High-resolution 2-DE analysis of human atrial tissue revealed that AF is associated with changes in structural proteins and an important number of HSPs. The lower expression of the structural protein fibulin-1 in atrial tissue from AF patients might reflect the myocardial structural changes that take place in the arrhythmia.
García
Angel
A
Departamento de Farmacoloxía, Facultade de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. angel.garcia@usc.es
Eiras
Sonia
S
Parguiña
Andrés F
AF
Alonso
Jana
J
Rosa
Isaac
I
Salgado-Somoza
Antonio
A
Rico
Trinidad Yolanda
TY
Teijeira-Fernández
Elvis
E
González-Juanatey
José Ramón
JR
D000368:Aged; D000369:Aged, 80 and over; D020517:Atrial Appendage / Q000737:chemistry / Q000378:metabolism*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015536:Down-Regulation / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D020543:Proteome / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002135:Calcium-Binding Proteins; D020543:Proteome; C060820:fibulin