title: Increased myocardial GRP94 amounts during sustained atrial fibrillation: a protective response?
abstract: BACKGROUND
  Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regulated protein GRP94, which is essential for cell viability, occur in the presence of chronic atrial fibrillation.
  
  
  RESULTS
  Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immunologic approach. In goats, atrial fibrillation was induced and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels doubled 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 cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase occurred 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 atria is comparable to GRP94 levels observed in perinatal goat myocardium. However, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas inducible 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 fibrillating atrial myocytes, which may be related to the appearance of a protective phenotype.
authors.affiliation: CNR Unit for Muscle Physiology and Physiopathology, Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vitadello
authors.forename: J
authors.initials: J
authors.lastname: Ausma
authors.forename: M
authors.initials: M
authors.lastname: Borgers
authors.forename: A
authors.initials: A
authors.lastname: Gambino
authors.forename: D C
authors.initials: DC
authors.lastname: Casarotto
authors.forename: L
authors.initials: L
authors.lastname: Gorza
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002908:Chronic Disease; D004554:Electric Countershock; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006041:Goats; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C018551:glucose-regulated proteins; D002118:Calcium