Heart structural gene causes sudden cardiac death

Heart structural gene causes sudden cardiac death

The presence or absence of the CAP2 gene causes sudden cardiac death in mice, according to new research. In particular, the absence of the gene interrupts the animal's ability to send electrical signals to the heart to tell it to contract, a condition called cardiac conduction disease. The study was published in Scientific Reports.

"Since humans have the same CAP2 gene, what we learn from the mice could advance our understanding of heart disease" author said.

The CAP2 gene's class of protein, while known to regulate the structure or cytoskeleton of the heart, is not usually associated with cardiac conduction because this function is governed by a different family of proteins associated with cell communication. 

Using a mouse model in which the team deleted the CAP2 gene, they found that most newborn males died suddenly, soon after weaning. The males were also prone to eye infections, and their eyes developed incorrectly and could not efficiently flush away debris. The knockout mice were also smaller in overall body size. Though rare, some of the mice also developed hearts that were overly large.

The knockout mice also exhibited arrhythmia that worsened over four to five days. Heart block happens when the heart atriums contract, but the ventricles do not get the signal to contract. As a result, the mouse hearts missed a few beats at first, and then stopped completely. This condition is called sudden cardiac death, which is distinct from a heart attack caused by clogged arteries impeding blood supply to the heart. In this experiment, there were no observable effects of a missing CAP2 gene on the female newborns.

Studies of some children .with a rare developmental problem, called 6p22 syndrome, hint that this gene is associated with similar cardiac issues in people. These children have deep-set eyes and cardiac problems that are not well defined. "Almost all of these children are born with a deletion of one of their copies of the CAP2 gene," author noted.

Knowing this connection, the researchers generated mice that would exhibit only cardiac conduction disease (CCD). They reinstated the gene but this time engineered it so they could knock it out again, but this time only in the hearts of the mice.

The mice once again developed CCD, leading to sudden cardiac death from complete heart block, but there was an extra surprise this time. The female newborns also died of CCD. "That's a puzzle for us. We'd be interested in studying why the gender specificity for CAP2-related sudden cardiac death goes away when we knock the gene out just in the heart," author said.

The team says that the study increases the understanding of how the CAP2 gene affects heart disease, but it also raises new questions that underline the need for further research heart disease and why it's a major cause of death in humans.