inositol-1-4-5-trisphosphate and Heart-Valve-Diseases

We examined whether patients with atrial fibrillation (AF) have alterations in atrial inositol 1,4,5 trisphosphate receptors (IP3 receptors).. Abnormal intracellular Ca2+ homeostasis occurs in chronic AF. The intracellular Ca2+ concentration is regulated by ryanodine and IP3 receptors. We recently reported alterations in ryanodine receptors in atrial tissue from patients in chronic AF.. We analyzed IP3 receptor expression in the right atrial myocardium from 13 patients with mitral valvular disease (MVD) with AF (MVD/AF), five patients with MVD who had normal sinus rhythm (MVD/NSR) and eight control patients with NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on atrial tissue.. The relative expression level of IP3 receptor protein was significantly greater in MVD/AF (0.75 +/- 0.26) than it was in MVD/NSR (0.42 +/- 0.13, p < 0.01), and both were significantly above control (0.14 +/- 0.08). The relative expression level of IP3 receptor messenger RNA was significantly greater in the MVD/AF group (0.028 +/- 0.008) than it was in the control group (0.015 +/- 0.004, p < 0.01), but patients with MVD/AF did not differ from patients with MVD/NSR (0.020 +/- 0.006). The relative expression levels of IP3 receptor protein and messenger RNA were higher in patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge pressure > or = 10 mm Hg and right atrial pressure > or = 5 mm Hg. Inositol 1,4,5 trisphosphate receptors were over-expressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD.. Since chronic mechanical overload of the atrial myocardium increased IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca2+ homeostasis and initiating or perpetuating AF.

Topics: Aged; Atrial Fibrillation; Atrial Function; Calcium Channels; Chronic Disease; Female; Heart Atria; Heart Valve Diseases; Humans; Immunoblotting; Immunohistochemistry; Inositol 1,4,5-Trisphosphate; Inositol 1,4,5-Trisphosphate Receptors; Male; Middle Aged; Mitral Valve; Myocardium; Pulmonary Wedge Pressure; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Up-Regulation