Enzyme Could Explain Link Between Diabetes And Heart Attack Death
February 16, 2013

Enzyme Could Explain Link Between Diabetes And Heart Attack Death

redOrbit Staff & Wire Reports — Your Universe Online

The over-activation of a vital heart enzyme leads to the death of pacemaker cells, abnormal heart rhythm, and an increased risk of sudden cardiovascular death in diabetic mice, researchers have discovered in a study that could shed new light on the relationship between the two ailments.

More than eight percent of the U.S. population has diabetes, and heart attack is the primary cause of death in those individuals, according to researchers from the University of Iowa. In fact, the risk of heart attack-related death is nearly double for those individuals versus non-diabetics, but the exact biological causes of that phenomenon have remained unclear, they explained.

"Many studies have shown that patients with diabetes are at especially high risk for dying from a myocardial infarction (heart attack). Our study provides new evidence that this excess mortality could involve a pathway where oxidized CaMKII enzyme plays a central role," Dr. Mark Anderson, senior author of the research, as well as professor, chair and department executive officer of internal medicine, said in a statement Friday.

Five years ago, Dr. Anderson and his colleagues discovered CaMKII (calcium/calmodulin-dependent protein kinase II) is activated by oxidative stress -- an increase in the level of so-called reactive oxygen species (ROS) that can be damaging to cells and can be caused by diabetes.

Now, in a study published in the latest edition of the Journal of Clinical Investigation, Iowa researchers have linked oxidation-based activation of that enzyme with an increased risk of death following a heart attack, with diabetes being the common thread.

"Our findings suggest that oxidized CaMKII may be a 'diabetic factor' that is responsible for the increased risk of death among patients with diabetes following a heart attack," Dr. Min Luo, a cardiology fellow in the UI Department of Internal Medicine and lead author of the new research, explained.

According to the university, Luo and her colleagues used a mouse model of diabetes to help establish the link between that disease and heart attack-related fatalities. Their work demonstrated the heart rates of diabetic mice slowed dramatically, and they, like people, were twice as likely to die following a heart attack versus non-diabetic rodents.

“Evidence from the diabetic mice suggested that the excess deaths following heart attack was due to heart rhythm abnormalities, prompting the team to investigate the heart's pacemaker cells, which control heart rate,” the university explained. “Looking at the diabetic mice, the team found that pacemaker cells had elevated levels of oxidized CaMKII enzyme and more cell death than pacemaker cells in non-diabetic mice. The levels of oxidation and cell death were further increased in the diabetic mice following a heart attack.

“When the team blocked oxidation-based activation of the enzyme, fewer pacemaker cells died, and the diabetic mice maintained normal heart rates and were protected from the increased death risk following a heart attack,” it added. “The findings suggest that preventing or reducing activation of the CaMKII enzyme in specific heart cells may represent a new approach for reducing the risk of death due to heart attack in patients with diabetes.”