Varying levels of a heart protein associated with variations in electrical stability
FRIDAY, Feb. 24 (HealthDay News) -- A body clock-dependent protein is associated with variations in electrical stability in the heart, which may explain why people are at higher risk of sudden cardiac death in the morning, according to research published online Feb. 22 in Nature.
After making the serendipitous discovery that kruppel-like factor 15 (Klf15) expression exhibited circadian rhythmicity in the heart, Darwin Jeyaraj, M.D., from the Case Western Reserve University in Cleveland, and colleagues investigated whether Klf15 was responsible for the observed rhythmic variation in repolarization associated with a higher risk of ventricular arrhythmias in the morning.
The researchers found that Klf15 controlled the expression of Kv channel-interacting protein 2, a regulatory subunit important for generating the transient outward potassium current. The Klf15 gene contained binding sites for circadian clock proteins. Mice with an excess or deficiency of Klf15 had abnormal repolarization and were more susceptible to developing ventricular arrhythmias.
"Our study provides the first mechanistic link between endogenous circadian rhythms and the cardiac electrical instability that is most often associated with sudden cardiac death in humans," Jeyaraj and colleagues conclude.
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