Over 500 million people worldwide carry a genetic mutation that disables a common metabolic protein called aldehyde dehydrogenase 2 or ALDH2. The mutation, which predominantly occurs in people of East Asian descent, leads to an increased risk of heart disease and poorer outcomes after a heart attack.
Now researchers at the Stanford University School of Medicine have learned specifically how the mutation affects heart health. They did so by comparing heart muscle cells made from induced pluripotent stem cells, or iPS cells, from people with the mutation versus those without the mutation. The use of heart muscle cells derived from iPS cells has opened important doors for scientists because tissue samples can be easily obtained and maintained in the laboratory for study.
The study showed that the ALDH2 mutation affects heart health by controlling the survival decisions cells make during times of stress. It is the first time ALDH2, which is involved in many common metabolic processes in cells of all types, has been shown to play a role in cell survival.
“This study is one of the first to show that we can use iPS cells to study ethnic-specific differences among populations. These findings may help us discover new therapeutic paths for heart disease for carriers of this mutation,” said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute. Dr. Wu is working now to start a biobank of iPS cells from about 1,000 people of many different ethnic backgrounds and health histories. This will help physicians to understand the disease process at a population level.
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