Monday, March 11, 2013
SDSU researchers work independently and collaboratively to find cures for heart disease.
Chris Glembotski, center, with students at the SDSU Heart Institute. Photo: Lauren Radack
Think of it as an investment in the human race. At San Diego State University, hundreds of years (in lab hours) and hundreds of millions of dollars have been devoted to curing the number one killer of men and women worldwide—heart disease.
The mission continues, led by four SDSU researchers whose combined efforts have gained international recognition and uninterrupted funding from the National Institutes of Health.
The best labs at the nation’s leading research institutions compete for funding from agencies such as NIH, and fewer than 20 percent of applicants receive them. Count San Diego State heart researchers among those elite awardees.
In the Donald P. Shiley BioScience Center, the SDSU Heart Institute and the Integrated Regenerative Research Institute, these researchers work independently and collaboratively to find cures for heart disease.
Roberta Gottlieb, M.D., and her team at the Shiley BioScience Center are pursuing significant discoveries that relate infection and inflammation to cardiovascular disease.
Just as peptic ulcers, once blamed on stress and diet, were eventually traced to the H. pylori bacterium, evidence now indicates that heart disease and strokes may be caused by common infections leading to inflammation within arteries.
A current study of young adult Native Americans and Hispanics by the Shiley BioScience Center is designed to explore links between periodontal disease and heart disease. The potential ramifications are staggering: Low-cost dental care and education could prevent heart attacks 20 years down the line, saving untold lives and health care dollars.
“If our hypothesis is correct,” Gottlieb said, “we will be the first to directly demonstrate a causal relationship between oral hygiene and atherosclerosis.”
The Shiley BioScience Center is also recognized for research on autophagy, a cellular process of breakdown and recycling. In collaboration with cardiac transplant surgeon Robert Mentzer Jr., SDSU researchers have shown that autophagy is activated in humans undergoing cardiac surgery and is essential for protecting the heart during a heart attack.
The role of proteins
Biologist Chris Glembotski, director of the SDSU Heart Institute, heads a team working to boost the heart’s natural protective processes—an important step toward the development of treatments aimed at reducing the damage caused by heart disease.
Heart Institute researchers in Glembotski’s group have made great progress in their efforts. They have discovered that heart disease damages proteins in the heart, causing them to misfold, as in neurodegenerative illnesses, such as Alzheimer’s and Parkinson’s diseases. The misfolding results in life-threatening loss of heart tissue and function.
Glembotski’s team found a gene in the heart that reduces damage by improving protein folding. Recently, they designed a new therapy for boosting the expression of this gene in the region of the heart most affected by heart disease.
“Our approach is significant because it enhances the heart’s own protective processes, but only in the diseased portion of the heart, which improves its safety and efficiency,” Glembotski said.
Equally exciting, Heart Institute researchers are using this approach in collaboration with other scientists to boost natural protective processes in the brain, a promising direction in the treatment of neurodegenerative diseases.
Tiny cardiac models
Sanford Bernstein, Ph.D., also a funded heart researcher, studies fruit flies to learn more about cardiac function in humans.
Although a fly heart is structurally different from the human heart, it’s a relevant model for exploring the molecular basis of heart muscle contraction, a particular focus of Bernstein’s lab. The team also studies how protein mutations known to cause neurological diseases, such as Alzheimer’s and Huntington’s, affect heart structure and function.
Bernstein’s lab has been successful in expressing heart-protective proteins that ensure normal structure and function in mutant fly hearts. Next, they hope to determine the molecular interactions that go awry in abnormal human heart proteins, resulting in disease.
“I derive great pleasure and motivation in seeing the undergraduates, graduate students and postdoctoral fellows in our lab gain the skills and insights needed to solve these global problems,” Bernstein said.
Mark Sussman’s approach to heart disease leverages the body’s ability to heal itself. He is director of SDSU’s Integrated Regenerative Research Institute, where researchers work to understand the processes of heart protection and regeneration with a goal of discovering
Using cardiac stem cells from human heart-failure patients, researchers in Sussman’s laboratory replicated them and then applied a molecule known as Pim-1 to improve the regenerative potential of damaged cells.
“With the help of Pim-1, these aged stem cells grow faster and are more resistant to dying,” Sussman said. “When introduced back into the damaged region of the heart, the newly restored stem cells enhance repair and regeneration by forming new heart tissue and improving the contraction force of the heart beat.”
With so many NIH-funded studies and so much collaborative work just in the field of cardiovascular research, it’s no wonder San Diego State is increasingly renowned as a fertile environment for ground-breaking basic research.