- Oxidative stress that occurs following a heart attack or in heart diseases, is the primary reason for damage to heart tissue.
- The stress causes over-accumulation of reactive oxygen molecules that derail the cells normal ability to function.
- ATF6, is a naturally occurring protein in the heart cells that helps to promote the natural ability of heart cells to protect itself from damage caused by stress.
A protein found in the heart cells is believed to play a critical role in the ability of cardiac cells to combat heart disease and recover from a heart attack.
The findings are according to a new study led by San Diego State University molecular cardiologist Christopher Glembotski, director of the SDSU Heart Institute.
The protein, known as ATF6, occurs naturally in all cells in the human body and appears to promote the natural ability of heart cells to protect itself from damage induced by stress.
Oxidative stress is the main reason for heart damage during heart attacks and heart disease. This stress is often caused by an overabundance of reactive oxygen molecules that derail the cell's normal ability to function.
Endoplasmic reticulum (ER) stress causes the accumulation of misfolded proteins in the ER and research has shown that the protein ATF6 responds to stress by activating the transcription factor, ATF6 (activating transcription factor 6 alpha), which induces ER stress response genes.
Heart attacks and heart diseases induces the ER stress response and previous studies in mice, have shown that during heart attacks, ATF6 is called into action, but its function in the heart was not known.
Role of ATF6
For the study, researchers investigated a strain of mice lacking the gene that codes for the production of ATF6.
They found that when these mice suffered from heart disease, the damage caused was more extensive damage than mice with normally functioning versions of the gene.
The protein ATF6, also activated a cascade of stress-response genes. These genes produced an enzyme known as catalase.
The functions of catalase include:
- acting as an antioxidant and neutralizing harmful reactive oxygen molecules
- reducing cellular stress and preventing proteins from misfolding
Restoring ATF6 in Aged Mice
As the mice ages, they progressively lose ATF6, and their hearts become more prone to damage during a heart attack.
In an effort to arrest this age-related effect, researchers used drug based on gene therapy to restore ATF6 production in heart cells of aged mice. The older mice who received the drug showed less damage following a heart attack.
"These cellular mechanics should work very much the same way in humans," Glembotski said.
"It seems to be an adaptive response of the heart that is lost with age," Glembotski said. "We think that, like the mice, human heart cells usually make some ATF6, but if they could make more--like in the young heart--the heart would be more resistant to heart disease."
ATF6 plays a critical role in initiating a process that reduces the damage caused by ischemia/reperfusion (I/R). I/R occurs when blood rushes back into tissue after a heart attack.
Ways to Boost AFT6 Production
Exercise may be the simplest way to naturally boost ATF6 production in the heart cells.
"Our preliminary studies show that exercise might naturally boost endogenous ATF6 and help prevent damage from I/R," Glembotski said.
Another way was to use gene therapy to boost naturally occurring ATF6. This could be especially effective for older people whose natural protection against cellular stress has waned.
"As we age, the adaptive stress response in the heart decreases," Glembotski said. "If we can deliver new versions of these genes to the heart, we could bring back some of that protection that you naturally have when you are young."
The findings appear in the journal Circulation Research.
- Christopher Glembotski et al. ATF6 Decreases Myocardial Ischemia/Reperfusion Damage and Links ER Stress and Oxidative Stress Signaling Pathways in the Heart. Circulation Research ; (2017) doi.org/10.1161/CIRCRESAHA.116.310266