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Stem Cells in Focus

Connecting Genetics and Heart Disease

By Maya Chaddah | August 5, 2014
Expert Contributor: Chad Cowan, PhD

Scientists and clinicians have long suspected and recently confirmed that a person’s genetic makeup contributes to the likelihood of their having a heart attack. However, there has remained a gap between our knowledge of genetic indicators and medicine; a gap that Dr. Chad Cowan, of Harvard University, is trying to bridge with stem cell research.

Stem Cells in Focus Webcast

2014-07-31 Cowan Photo_crop

Connecting Genetics and Heart Disease

Chad Cowan, PhD, Harvard University, USA

Learn more about the research and its potential, and pose your questions directly to Dr. Cowan, during a live public webcastThursday, August 7 at 1:30 pm ET (USA).

According to Dr. Cowan,what we know about genetics is not the full picture. We do not yet fully understand how a given gene functions within a cell or how it affects other genes. He believes the study of induced pluripotent stem cells (iPS cells) – adult stem cells that are reprogrammed in such a way that they can generate most other cell types found within the body – will result in better and more personalized approaches to treat  heart attacks.

The foundation of Dr. Cowan’s research began over 60 years ago, with the Framingham Heart Study. The death rates from heart disease and heart attacks had been increasing steadily since the beginning of the century, but not much was known about the general causes. The objective of the study was to identify contributing factors by following the development of the disease over a long period of time in a large group of participants.

The study began in 1948 with 5,209 citizens, aged 30-62, from Framingham, Massachusetts, USA, who had not yet developed overt symptoms of cardiovascular disease or suffered a heart attack or stroke. They each had an initial physical examination and lifestyle interview, and then returned every two years thereafter for physical examinations, medical histories and laboratory tests.  In 1971, the study was expanded to include a second generation, the original participants’ adult children and their spouses. The study continues to enroll a third generation of participants and to increase its diversity.

Three years ago, Dr. Cowan’s group teamed up the Framingham Heart Study to learn more about how different genetic factors influence cholesterol levels in the blood, and to look for—and test—drugs that might help lower blood cholesterol. Using a technique called cellular reprogramming, his group made iPS cells from over 60 second generation study participants, which were then used to create patient-specific liver cells and heart cells.

Dr. Cowan’s team had earlier identified a variant of the SORT1 gene that influences cholesterol levels in the blood and, thus, risk of heart disease. They have since proposed that the variant increases the amount of the SORT1 gene product (called Sortilin 1) in the liver, and that increasing Sortilin 1 levels reduces the cholesterol secreted into the blood, decreasing the likelihood of a heart attack. In bearing out this hypothesis, they are studying iPS cell-derived liver cells with and without the gene variant to determine whether there is a difference in cholesterol levels.

Dr. Cowan believes his iPS cells, and the liver and heart cells made from them, together with study participants’ medical histories, will continue to improve our understanding of heart disease, inform the development of new drugs and enable us to screen drugs for safety and efficacy against individual patients.  

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