Many Asians carry a mutation that causes their faces to flush when they drink alcohol. The affected gene is called ALDH2, and it also plays a role in cardiovascular health. Carriers are more susceptible to coronary artery disease and tend to recover more poorly than non-carriers from the damage caused by a heart attack. Now Stanford cardiologist Joseph Wu, MD, PhD, and postdoctoral scholar Antje Ebert, PhD, have learned why.
The researchers used a type of stem cell called an induced pluripotent stem cell, or iPS cell, to conduct the study. The stem cells are made from easily obtained tissue like skin, and they can be coaxed in the laboratory to become other types of tissue, like heart muscle cells. It's one of the first times iPS cells have been used to examine ethnic-specific differences among populations. The research was published yesterday in Science Translational Medicine.
From our release:
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. In particular, ALDH2 activity, or the lack of it, influences whether a cell enters a state of programmed cell death called apoptosis in response to stressful growing conditions. [...]
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. Until recently, researchers had to confine their studies to genetically engineered mice or to human heart cells obtained through a heart biopsy, an invasive procedure that yields cells which are difficult to keep alive long term in the laboratory.
You've likely read about Wu's previous work with heart muscle cells derived from iPS cells. Now he's shown iPS cells are also a good way to compare the effect of genetic differences among populations, and he has big plans. More details about his plans from our release:
Wu is working to start a biobank at the Stanford Cardiovascular Institute of iPS cells from about 1,000 people of many different ethnic backgrounds and health histories. “This is one of my main priorities,” he said. “For example, in California, we boast one of the most diverse populations on Earth. We’d like to include male and female patients of major representative ethnicities, age ranges and cardiovascular histories. This will allow us to conduct ‘clinical trials in a dish’ on these cells, a very powerful new approach, to learn which therapies work best for each group. This would help physicians to understand for the first time disease process at a population level through observing these cells as surrogates.”
Previously: Induced pluripotent stem cell mysteries explored by Stanford researchers, A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells and “Clinical trial in a dish” may make common medicines safer, say Stanford scientists
Photo by Nicholas Raymond
