A Gene That Brakes Blood Vessel Growth Explains Endurance Athletes' Edge

Muscle endurance depends on fuel delivery. Oxygen and nutrients reach muscle cells through capillaries - the finest blood vessels in the body - and the same system removes carbon dioxide and metabolic waste. More capillaries mean better supply, faster clearance, and greater capacity to sustain high-intensity effort over time. Elite endurance athletes typically have substantially higher capillary density in their muscles than sedentary individuals. Training explains part of this, but genetics clearly plays a role. Identifying the specific genes involved has been an active area of investigation.

A study led by researchers at Lund University, drawing on muscle biopsies and DNA from more than 600 Swedish participants, has now identified a specific genetic variant linked to capillary density in muscle tissue. The gene is RAB3GAP2, and its product is a protein that acts as a molecular brake on blood vessel formation. People who carry the variant produce less of this braking protein - and consequently form more capillaries.

From Swedish Muscles to International Cohorts

The initial discovery phase examined muscle tissue and genetic data from the Swedish cohort. The variant showed a clear statistical association with capillary density. The researchers then looked at how it was distributed across populations with different athletic profiles.

Swedish elite cross-country skiers - a classic endurance population - carried the variant at roughly 10 percent frequency, compared to approximately 5 percent in non-athletes. That is a doubling of prevalence in a group specifically selected for superior aerobic capacity over long distances. Among athletes in explosive sports, where strength and rapid energy delivery matter more than sustained oxygen transport, the variant was substantially rarer. Among world-class sprinters from Jamaica - perhaps the most intensively studied explosive-sport population in genetics research - the frequency fell below 1 percent.

The international validation component of the study replicated the Swedish findings in independent athlete cohorts from six countries across Europe, America, and Asia. The variant did not emerge as a significant factor in African athlete cohorts, suggesting either population-specific differences in genetic architecture or simply different pathways to elite athletic performance across diverse genetic backgrounds.

The Molecular Mechanism

"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," said Ola Hansson, researcher in physiology at Lund University.

The brake is not fixed. High-intensity interval training reduces the activity of the braking protein in people without the genetic variant - essentially achieving through exercise what the variant achieves genetically. When the protein's activity decreases, cells that form blood vessels become more active, and tissue remodeling signals increase. This molecular pathway may partly explain the well-established observation that interval training improves cardiovascular fitness even in people with average genetic profiles.

"It's also the reason why training improves both performance and metabolic health," said Kristoffer Strom, a researcher at Lund University involved in the study.

A Trade-off Worth Understanding

The favorable variant is not purely advantageous. The same mechanism that promotes rapid vessel growth is also associated with heightened inflammatory response and a modestly elevated risk of muscle injuries. This trade-off has parallels in other athletic genetics findings - the traits that confer competitive advantage in specific conditions often carry costs in different contexts.

"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," Strom said.

Understanding this balance has practical implications for sports medicine, where the goal is to optimize training adaptation while managing injury risk. It also has potential implications for public health more broadly, since capillary density affects metabolic function in ways relevant to conditions like type 2 diabetes.

A Drug Target on the Horizon

The research team has initiated a collaboration with AstraZeneca to explore whether an inhibitor of the braking protein could increase muscle capillary density in patients with muscle insulin resistance - a condition that reduces the ability of skeletal muscle to absorb glucose and is central to type 2 diabetes. Such a drug does not currently exist. The hypothesis is that suppressing the brake sufficiently to stimulate new capillary formation could improve glucose uptake by muscles without the exercise stimulus that many diabetic patients cannot easily sustain.

That application remains in the early exploratory stage. The current study established the genetic and physiological mechanism; translating it into a therapeutic target requires substantial additional work.

Limitations

The variant appears in a minority of the population - roughly 5 percent overall - which limits its predictive utility for individual athletes or patients. The study identified an association between the variant and capillary density; the mechanistic chain from gene to vessel density to athletic performance involves multiple steps, not all of which were directly measured. The absence of the finding in African cohorts requires investigation before claiming global generalizability.