Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation.
OBJECTIVE
Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling.


METHODS
Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (> 8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Cox's MAZE surgery (n = 12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression.


RESULTS
L-type calcium channel alpha 1 and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (-57%, p = 0.01 and -28%, p = 0.04, respectively) and protein contents (-43%, p = 0.02 and -28%, p = 0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF.


CONCLUSIONS
Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF.
Brundel
B J
BJ
Department of Cardiology, University Hospital Groningen, The Netherlands.
van Gelder
I C
IC
Henning
R H
RH
Tuinenburg
A E
AE
Deelman
L E
LE
Tieleman
R G
RG
Grandjean
J G
JG
van Gilst
W H
WH
Crijns
H J
HJ
D000368:Aged; D001281:Atrial Fibrillation / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000032:analysis / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000032:analysis / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D019831:Sodium-Calcium Exchanger / Q000235:genetics; D013997:Time Factors; D000099211:Phospholamban
D002118:Calcium; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D020033:Protein Isoforms; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban