Postoperative atrial fibrillation (poAF) is a common complication of cardiothoracic surgery with an incidence between 10 and 50%. This condition typically peaks on day 2-3 following surgery, and is associated with excessive hospitalization time, increased risk of stroke, and an increase in patient morbidity. Whereas progress has been made towards understanding the pathogenesis of AF in general, very little remains known about the molecular mechanisms underlying poAF. Our preliminary data reveal perturbed intracellular Ca handling in atrial biopsies from patients with poAF. Increased activity of the ryanodine receptor Ca release channel was found in atrial myocytes of patients with poAF and a novel mouse model of poAF. Our data suggest that enhanced RyR2 activity is caused by altered levels of `Striated Muscle Preferentially Expressed Protein Kinase' (SPEG) in atria of patients and mice with poAF. The long-term goal of this project is to elucidate the molecular and cellular mechanisms underlying poAF development. We will test the hypothesis that abnormal Ca release via RyR2 due to altered SPEG phosphorylation causes enhanced susceptibility to poAF.
The proposed work will elucidate the molecular basis of altered intracellular calcium handling in patients and mice with postoperative atrial fibrillation. In particular, the cellular mechanisms underlying aberrant sarcoplasmic reticulum calcium handling will be studies.
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