SAN DIEGO STATE RESEARCHERS MIMIC CARDIAC CELL DEFENSES TO REDUCE DAMAGE FROM HEART ATTACKS

Contact:

Lorena Nava
SDSU Marketing & Communications
Tel: (619) 594-3952 office, (619) 309-5179 cell
lnava@mail.sdsu.edu

Chris Glembotski, Photo Credit: Lauren Radack

SAN DIEGO (Thursday, August 10, 2006) – Researchers at San Diego State University's Heart Institute have developed an innovative way to activate a gene program that imitates a cardiac cell's natural stress response system, a tool that may eventually be used to reduce or even prevent damage from heart attacks.
 
The researchers genetically modified the hearts of mice so they would express a novel form of a protein called ATF6. This caused the heart muscle cells' endoplasmic reticulum to produce eight to 15 times the amount of stress-protection proteins than produced by non-modified heart muscle cells. The genetically modified mouse hearts also exhibited faster and more complete recovery from heart attacks, as well as half the cell death and damage, compared to non-modified hearts.

"Our discovery of the importance of this gene program is a promising new lead toward development of new therapeutics, and potentially a proactive treatment for people at risk of a heart attack," said Chris Glembotski, the project's lead researcher and director of the SDSU Heart Institute. "It might reduce the chances of a heart attack, or it could decrease the damage to the heart muscle should a heart attack occur."

The role of the ATF6-activated gene program in the heart was first realized when the researchers, in a separate study, discovered that the endoplasmic reticulum (the cellular location for the synthesis of many vital proteins) in heart muscle cells produces a number of protective proteins when exposed to a lack of oxygen, the most dangerous effect of a heart attack.

The researchers' work appears in a pair of articles that culminated this month in Circulation Research, a leading cardiovascular science journal published by the American Heart Association.

"These studies give us a better understanding of how heart cells respond and adapt to the stress of a heart attack, and they provide evidence we can apply that knowledge to develop gene therapies that can reduce heart injury and save lives," Glembotski said.

Heart disease and heart attacks remain one of the United States' leading health problems. The American Heart Association estimates more than 1.2 million Americans will have their first or a recurrent heart attack this year. Approximately 479,000 of them will die.

While Glembotski hopes therapies based on the endoplasmic reticulum (ER) stress response eventually will reduce those numbers, he added that similar therapies could be developed to address other devastating injuries and health problems.

"These protective genes are expressed in most cell types," Glembotski said. "That means theoretically we could apply the same treatment methods for other situations, for example to brain cells to reduce damage from strokes. There are also implications ER stress response could play a role in fighting cancer and diabetes."

These studies of the ER stress response in the heart, which are funded by the National Institutes of Health, have just begun at SDSU. There are many more exciting avenues to explore, he said.

"Prior to these studies, this protective mechanism had not been studied in the heart," Glembotski said. "We have just completed a more comprehensive analysis of the effects of ATF6 on more than 30,000 different genes in the mouse heart, and we have begun to investigate the identities of all the genes that respond. We look forward to finding many new gene families that could provide us with much-needed information that will help in the development of better therapies in the future."

The SDSU research team, including Glembotski, SDSU biology professor Mark Sussman, research specialists Donna Thuerauf and Natalie Gude, and graduate students Joshua Martindale, Rayne Fernandez and Ross Whittaker, began their studies of ER stress response in 2004.

The SDSU Heart Institute is sponsored by SDSU’s College of Sciences and College of Health and Human Services and includes approximately 30 faculty members from a number of health-related disciplines. Its mission is to promote research and teaching programs relating to heart and cardiovascular system performance in health and disease, and to increase awareness of cardiovascular disease and its prevention in the greater San Diego area.

SDSU is the oldest and largest institution of higher education in the San Diego region. Founded in 1897, SDSU offers bachelor’s degrees in 81 areas, master’s degrees in 72 and doctorates in 16. SDSU’s nearly 33,000 students participate in academic curricula distinguished by direct faculty contact and an increasingly international emphasis that prepares them for a global future. For more information, visit www.sdsu.edu.

###