Researchers identify a genetic brake for the formation of blood vessels in muscles

In an international study, researchers at Lund University in Sweden have identified a gene variant that controls the body's capability to form new blood vessels in muscles – a mechanism that affects physical performance, health and recovery. The favorable gene variant is considerably more common among top athletes in endurance sports, compared with both top athletes in explosive sports and non-athletes.

Key facts

• Discovery: The gene RAB3GAP2 regulates the number of blood vessels in muscles.

• Significance: Affects muscle function, endurance and metabolism.

• Sports: The favourable variant is more common among top athletes in endurance sports and less common among sprinters.

• Training: High-intensity training reduces the gene's activity and can increase blood vessel growth.

• Future: Potential applications in individualised training, rehabilitation and metabolic health.

Capillaries are the body's smallest blood vessels and act as the muscles' supply lines. The more capillaries a muscle has, the better the supply of oxygen and nutrients to the muscle cells – and the more effectively waste products can be removed. This is of great importance for the body's physical performance capacity, metabolism and recovery. For athletes in endurance sports, it is therefore an advantage to have more capillaries compared to athletes in explosive sports, where muscle strength and fast access to energy are the crucial factors.

In the study in question, the researchers started by examining muscle and DNA from just over 600 Swedes. This investigation identified a genetic variant that could be linked to the number of capillaries in the musculature. The researchers also noted that athletes in endurance sports, i.e. Swedish cross-country skiers, were twice as likely to carry the genetic variant – about ten per cent compared to five per cent among non-athletes. The variant affects a gene that controls the protein that regulates how blood vessels are formed around muscle fibers. If you have the genetic variant, less of the protein is produced which means more new blood vessels are formed.

It could be said that we have identified a genetic brake for the new formation of blood vessels in muscles. When the brake is weak, more capillaries are formed. This improves the transport of oxygen and therefore endurance." 

Ola Hansson, researcher in physiology, Lund University

The researchers then went on to conduct a large international study, which examined the DNA from top athletes in six countries. The results of the Swedish study could be confirmed in independent international athlete cohorts and were identified among athletes in Europe, America and Asia – but not in Africa. It was also discovered that the variant was extremely rare among athletes in explosive sports, for example less than one per cent of world-class sprinters from Jamaica carry the variant.

At the same time, the study showed that the brake function is not static. It is possible to reduce it yourself through high-intensity interval training. You then "release the brake" and reduce activity of the braking protein that controls the new formation of blood vessels. When the activity of the protein decreases, this stimulates the growth of cells and their capacity to form new blood vessels, while the body increases production of the signal substance that controls the rebuilding of tissue.

"It's also the reason why training improves both performance and metabolic health," says Kristoffer Ström, researcher at Lund University.

The genetic variant that promotes rapid vessel growth is also linked to an increased inflammatory response and in certain contexts a higher risk of muscle injuries. The performance advantage thus entails other challenges – an important balance to understand in both sports medicine and public health.

"Training is a way to subject the body to controlled stress and thereby improve performance. You could look at the protein we identified as a volume control for the body's stress response. People with the genetic variation have the volume set a little higher to begin with – which increases the benefits of training. But if the volume is turned up too much you see the opposite effect – poorer recovery and an increased risk of injury," says Kristoffer Ström.

The researchers emphasize that the important discovery in the study mainly concerns the molecular mechanisms behind the adaptation of muscles to training. This knowledge can contribute to more individualized training programmes, better rehabilitation and perhaps new treatments for metabolic diseases.

"We have started a collaboration with Astra Zeneca to hopefully find an effective drug for muscle insulin resistance among diabetics – something that is not available at present. If we can develop an inhibitor that suppresses this brake protein sufficiently, the new formation of capillaries could mean an increase in the uptake of sugar in muscles," concludes Ola Hansson.