Posts Tagged ‘Blood doping’

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 Richard 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.”
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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, Brian Annex, M.D., and Zhen Yan, Ph.D. Svein Rotevatn, Haukeland University Hospital, Bergen, Norway, was also a member of the team.

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 Richard 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.”

 

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Article adapted by MD Sports from original press release.
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Contact: Richard Merritt
Duke University Medical Center 

The research team was supported by grants from the American Heart Association and the U.S. Department of Veterans Affairs

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A stunning discovery by German scientists may make blood doping and the treatment of severe anemia as easy as washing your hair.  

In the October print issue of The FASEB Journal (http://www.fasebj.org/), researchers show that the estimated 100,000 hair follicles on each person’s head have the potential to become erythropoietin (EPO) factories. EPO, the hormone primarily responsible for the creation of red blood cells, is used illegally to enhance athletic performance and is used legally to treat severe anemia associated with kidney failure and chemotherapy.

“The ultimate hope is that we’ll be able to up the production of natural EPO in our hair follicles whenever we need it, safely and at a low cost,” said Ralf Paus, senior author of the study. “Our study also highlights that ancient hormones are engaged in many more activities than conventional medical wisdom has assigned to them.”

Normally, EPO is created and released by the kidneys. When the kidneys fail, or when someone undergoes chemotherapy, this process is disrupted and severe anemia occurs. Today, most people are treated using synthetic EPO to bring red blood cells back to normal levels, but synthetic versions of this hormone are relatively expensive. Blood-doping athletes use synthetic EPO to help their bodies bring red blood cells to above-normal levels. This increased concentration of red blood cells allows the blood to deliver more oxygen to muscles than normal, significantly improving endurance and performance. The major danger in boosting the number of red blood cells above normal is that as the blood thickens with red blood cells, the possibility of heart attack increases.

“This study opens doors to an entirely new approach for treating EPO-related anemia,” said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. “The study also is important because it suggests that there is still much to learn about ‘well known’ processes in the body.”

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Article adapted by MD Sports Weblog from original press release.
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Source: Cody Mooneyhan
Federation of American Societies for Experimental Biology

The FASEB Journal (http://www.fasebj.org/) is published by the Federation of American Societies for Experimental Biology (FASEB) and is consistently ranked among the top three biology journals worldwide by the Institute for Scientific Information. FASEB comprises 21 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances biological science through collaborative advocacy for research policies that promote scientific progress and education and lead to improvements in human health.