Cardiac Death Controlled By Circadian Clock

Researchers have discovered a new link between the time of day and sudden cardiac death (SCD). Abnormal heart rhythms are the most common cause of sudden cardiac death, which happens most often in the morning hours, followed by a smaller peak during the evening hours. This phenomenon has been observed for years but doctors are just now beginning to understand the molecular reason.
The researchers found that Krupple-like Factor 15 (KLF15) links the body´s circadian rhythm to the heart´s electrical activity. Either an excess or a lack of KLF15 causes heart arrhythmia. A lack of KLF15, according to a recent press release, is seen in patients with heart failure while an excess of the protein causes electrocardiography (ECG) changes like in patients with Brugada syndrome, a genetic heart rhythm disorder.
Darwin Jeyaraj, MD, MRCP, assistant professor of medicine at Case Western Reserve University School of Medicine and lead author of the study, said “Our study identifies a hitherto unknown mechanism for electrical instability in the heart. It provides  insights into day and night variation in arrhythmia susceptibility that has been known for many years.”
SCD is the leading cause of death in the US killing 700 to 800 people per day. It is estimate SCD´s cause around 325,000 deaths annually, and accounts for 10,460 or 75.4 percent of all 13,873 cardiac disease deaths of 35 to 44 year olds.
The study observed the biochemistry of mice. The researchers discovered that KLF15 controls the level of a potassium channel-interacting protein (KChIP2) that affects the flow of potassium out of the cardiac myocytes.
The level of the KChIP2 protein changes throughout the daily circadian cycle and it changes the size of the potassium current in cardiac myocytes. While changes in the KLF15 affects the repolarization of the cardiac myocytes. The change in repolarization affects the time that allows the heart muscle to push the blood through the heart chambers. The time for repolarization is important because too much or too little time, also called long QT or short QT, causes arrhythmias in the heart causing the heart to pump inefficiently and possibly sudden death.
One of the authors Dr. Xander Wehrens says, “It is the first example of a molecular mechanism for the circadian change in susceptibility to cardiac arrhythmias.
The research was published in the journal Nature.

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