Hyperhomocysteinemia causes cardiac rhythm disturbances due to a shift in atrial and ventricular gap junction protein distribution

Abstract

Homocysteine (Hcy) is an amino acid byproduct in the metabolism of methionine. Hyperhomocyseinemia (HHcy) is associated with thromboembolic events. Hcy has been identified to correlate with atrial fibrillation and stroke in humans. The role of Hcy and its influence on atrial and ventricular gap junction proteins has been investigated. We hypothesize that changes in the Connexin (Cx) distribution and localization are responsible for cardiac arrhythmia. ECG was monitored in freely moving mice (Hcy‐diet for 12 weeks) with a subcutaneously implanted telemetric ECG probe. 2D transthoracic echocardiography was performed to assess regional wall motion abnormalities and ventricular diameter changes in M‐Mode. Immunoblotting was used for quantification, immunohistochemistry was used to visualize the localization of the gap junction proteins Cx 40, 43 and 45. A shift of Cx 43 to Cx 45 was seen in the ventricular myocardium, a loss of Cx 40 was detected in the atrial myocardium in HHcy animals. Arrhythmia, sudden cardiac death and left ventricular dysfunction along with right ventricular diameter changes were detected in the HHcy animal group.