Peripheral artery disease (PAD) affects 5 million individuals in the U.S. and is the leading cause of limb amputations. Doctors have long considered exercise to be the single best therapy for PAD, and now a new study helps explain why. Led by researchers at Beth Israel Deaconess Medical Center and published in this week's Online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), the findings demonstrate that a protein called PGC-1alpha plays a key role in the process.
"Exercise is a staple of healthy living," notes senior author Zoltan Arany, MD, PhD, an investigator in BIDMC's Cardiovascular Institute and Assistant Professor of Medicine at Harvard Medical School. "One of the many benefits of exercise, endurance exercise in particular, is the generation of new blood vessels in leg muscles." Known as angiogenesis, this naturally occurring process comes to the rescue when an injury or artery blockage leaves normal tissue starved for blood.
PAD is a common circulatory problem in which narrowed arteries reduce blood flow to the limbs. The end result is leg pain primarily encountered while walking. More seriously, PAD is also likely to be a sign of widespread accumulation of fatty deposits in the arteries, which may be reducing blood flow to the heart and brain as well as to the legs.
The PGC-1alpha molecule was first identified more than 10 years ago. Last year, Arany was part of a research team that discovered that when body parts are jeopardized by poor circulation, PCG-1alpha senses dangerously low levels of oxygen and nutrients and, in response, spurs the growth of new blood vessels. Knowing that muscle adapts to endurance-type exercise by triggering angiogenesis, Arany and his coauthors set out to better understand the mechanisms behind this orchestrated process, and to determine if PGC-1alpha had a hand in the outcome.
The researchers studied mice in cages equipped with electronically monitored running wheels. As predicted, voluntary exercise was found to lead to robust angiogenesis in mouse skeletal muscle. The investigators also found that the mice that were lacking PGC-1alpha failed to grow new blood vessels in response to exercise. Ultimately, their experiments demonstrated that exercise activates beta-adrenergic signaling, which leads to a robust induction of PGC-1alpha.