Study explains how exercise helps patients with peripheral artery disease

Dec 03, 2009

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.

" 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 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.

"Our data strongly suggest a new paradigm for the process of angiogenesis in response to exercise, demonstrating that upstream beta-adrenergic signaling, likely stemming from increased nerve activity, triggers angiogenesis," the authors write. (Interestingly, they add, this suggests that the use of beta blockers in patients with PAD might block some of the benefits of exercise. These medications are widely used to treat patients with coronary artery disease, and patients with PAD often have concurrent CAD.)

"With this study, we have found that the protein PGC-1 alpha can single-handedly transform muscle to be capable of greater endurance and increase the blood content of that muscle. Being able to increase vessel density could help wound healing and even prevent amputations in millions of patients with diabetes and vascular disease of the limbs," notes Arany. "Exercise remains one of the most effective interventions for a number of chronic diseases, including obesity, diabetes, atherosclerosis and neurodegenerative diseases. PAD is a leading cause of morbidity and the most common cause of limb amputation in the U.S. and yet even the best medical therapy available is less effective than simply walking daily."

Source: Beth Israel Deaconess Medical Center

Explore further: Mice study shows efficacy of new gene therapy approach for toxin exposures

add to favorites email to friend print save as pdf

Related Stories

Another way to grow blood vessels

Feb 21, 2008

Researchers at Dana-Farber Cancer Institute have found a previously unknown molecular pathway in mice that spurs the growth of new blood vessels when body parts are jeopardized by poor circulation.

Step out for PAD

Dec 15, 2008

You probably know that poor diet and lack of exercise can lead to dangerous deposits of fatty plaques in arteries. But it is not just the heart that is affected – blood flow can be blocked to the legs too, leading to pain ...

The Medical Minute--What is vascular disease?

Apr 09, 2008

In simplest terms, “vascular” is a word that refers to blood vessels, those little tubes called arteries and veins that carry blood throughout the body. Health professionals often describe blood vessels based on their ...

Heading circulatory disease off at the pass

Jul 17, 2008

Researchers at Oregon Health & Science University have devised an ultrasound imaging technique that picks up subtle early evidence of peripheral arterial disease (PAD) that current conventional tests miss.

Recommended for you

How Alzheimer's peptides shut down cellular powerhouses

Aug 29, 2014

The failing in the work of nerve cells: An international team of researchers led by Prof. Dr. Chris Meisinger from the Institute of Biochemistry and Molecular Biology of the University of Freiburg has discovered ...

User comments : 2

Adjust slider to filter visible comments by rank

Display comments: newest first

3432682
not rated yet Dec 03, 2009
I bet strength training exercise would be more beneficial than endurance exercise. Weight training is what builds lots of muscle, fast. I bet it also builds lots of blood vessels, or increases blood vessel capacity (or both). Anyhow, this is a very valuable article for those with PAD or diabetes - many millions of people.
moj85
not rated yet Dec 03, 2009
Can anyone actually find this paper? I searched PNAS but can't find it..