Increased myocardial GRP94 amounts during sustained atrial fibrillation - A protective response?

Background-Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regula ted protein GRP94, which is essential for cell viability, occur in the pres ence of chronic atrial fibrillation. Methods and Results-Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immuno logic approach. In goats, atrial fibrillation was induced and maintained fo r 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversi on was applied and followed by 8 weeks of sinus rhythm. GRP94 levels double d in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect to normal atria and returned to control levels in atrial myocardium of card ioverted goats. Immunohistochemical analyses confirm that GRP94 increase oc curred within cardiomyocytes. Significantly, increased levels of GRP94 were also observed in samples from human fibrillating atria. In the absence of signs of myocyte irreversible damage, the GRP94 increase in fibrillating at ria is comparable to GRP94 levels observed in perinatal goat myocardium. Ho wever, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas indu cible HSP70, a cytoplasm stress protein that is expressed in perinatal goat hearts at levels comparable to those observed in the adult heart, shows a significant increase in chronic fibrillating atria. Conclusions-Our data demonstrate a large, reversible increase in GRP94 in f ibrillating atrial myocytes, which may be related to the appearance of a pr otective phenotype.