New insights into muscle adaptation to exercise

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New insights into muscle adaptation to exercise

09 Nov 2004 http://www.medicalnewstoday.com/medicalnews.php?newsid=16072

Duke University Medical Center researchers have identified the skeletal

muscle changes that occur in response to endurance exercise and have

better defined the role of vascular endothelial growth factor (VEGF) in

creating new blood vessels, known as angiogenesis, in the process.

VEGF is a protein known to trigger blood vessel growth by activating

numerous genes involved in angiogenesis.

The researchers' new insights could provide a roadmap for medical

investigators as they seek to use VEGF in treating human conditions

characterized by lack of adequate blood flow, such as coronary artery

disease or peripheral arterial disease.

Using mice as animal models, the researchers found that exercise

initially stimulates the production of VEGF, which then leads to an

increase in the number of capillaries within a specific muscle fiber

type, ultimately leading to an anaerobic to aerobic change in the muscle

fibers supplied by those vessels. The VEGF gene produces a protein that

is known to trigger blood vessel growth.

The results of the Duke experiments were presented by cardiologist

Waters, M.D., Nov. 8, 2004, at the American Heart Association's

annual scientific sessions in New Orleans.

" It is known that exercise can improve the symptoms of peripheral

arterial disease in humans and it has been assumed that angiogenesis

played a role in this improvement, " Waters said. " However, the clinical

angiogenesis trials to date utilizing VEGF have been marginally

successful and largely disappointing, so we felt it would be better at

this point to return to animal studies in an attempt to better

understand the angiogenic process. "

The Duke team performed their experiments using a mouse model of

voluntary exercise. This experimental approach is important, they

explained, because most skeletal muscle adaptation studies utilize

electrical stimulation of the muscle, which is much less physiologic and

does not as closely mimic what would be expected in human exercise.

When placed in the dark with a running wheel, mice will instinctively

run, the researchers said. In the Duke experiments, 41 out of 42 mice

" ran " up to seven miles each night. At regular intervals over a 28-day

period, the researchers then performed detailed analysis of capillary

growth and the subsequent changes in muscle fiber type and compared

these findings to sedentary mice.

Mammalian muscle is generally made up of two different fiber types -

slow-twitch fibers requiring oxygen to function, and the fast-twitch

fibers, which function in the absence of oxygen by breaking down

glucose. Because of their need for oxygen, slow-twitch fibers tend to

have a higher density of capillaries. " Exercise training is probably the

most widely utilized physiological stimulus for skeletal muscle, but the

mechanisms underlying the adaptations muscle fibers make in response to

exercise is not well understood, " Waters said. " What we have shown in

our model is that increases in the capillary density occur before a

significant change from fast-twitch to slow-twitch fiber type, and

furthermore, that changes in levels of the VEGF protein occur before the

increased capillary density. "

" Interestingly, capillary growth appears to occur preferentially among

fast-twitch fibers, and it is these very fibers that likely change to

slow-twitch fibers, " Waters said. " Since exercise has the potential to

impact an enormous number of clinical conditions, therapeutic

manipulations intended to alter the response to exercise would benefit

from a more detailed understanding of what actually happens to muscle as

a result of exercise. "

The exact relationship between VEGF, exercise induced angiogenesis, and

muscle fiber type adaptation is still not clear and will become the

focus of the group's continuing research. The findings from the current

study, however, are providing important temporal and spatial clues to

the adaptability process.

" Our data suggests that angiogenesis is one of the key early steps in

skeletal muscle adaptation and may be an essential step in the

adaptability process, " Waters continued. " This understanding could be

crucial for designing new studies that can be performed to inhibit the

angiogenic response to exercise in order to directly test the links

between angiogenesis and skeletal muscle plasticity. "

The research team was supported by grants from the American Heart

Association and the U.S. Department of Veterans Affairs.

Other members of the Duke team were Ping Li, Annex, M.D., and Zhen

Yan, Ph.D. Svein Rotevatn, Haukeland University Hospital, Bergen,

Norway, was also a member of the team.