Cardiovascular disease is unlikely to be a concern for the many amazing athletes at this year's summer Olympics. This is because exercise capacity is related to heart function, and a strong healthy heart is important for pumping blood around the body during exercise. Being a good athlete and having a strong heart depends a lot on genetics, which can contribute half of the variation seen in human exercise capacity. Some other animal species have also evolved the ability to perform astounding feats of athleticism, often with very little training. However, in humans or animals from the wild it can be very difficult to separate the genetic basis for exercise capacity, heart function and cardiovascular disease from the effects of training and environment. Anja Bye and colleagues from the Norwegian University of Science and Technology therefore decided to examine this topic in rats artificially selected for running endurance.
Artificial selection is a way of mimicking natural selection in the lab. Every generation, individual rats with the best and worst running endurance were selected and bred together, generating lines with high and low capacities for running long distances. The authors knew that hearts from the athletic line could pump more blood than those from the unathletic line, because their hearts were bigger and their heart muscle fibres could contract more. They also knew that the low-capacity runners had risk factors for cardiovascular disease, like high blood pressure and elevated lipid levels in the blood. To better understand the underlying molecular basis for these differences, Bye and colleagues compared gene expression in the hearts of these high- and low-capacity rat lines.
By measuring the expression of 28,000 genes with gene chips, small microarray slides that quantify the expression of many different genes at once, the authors found that 1540 genes were differentially expressed between high- and low-capacity runners. Many genes were expressed at higher levels in the athletic line, which could explain how their hearts perform better than those of the unathletic line. Contraction and calcium signalling genes were more highly expressed, potentially explaining how their heart muscle fibres are better at contracting. Expression of fat metabolism genes was also enhanced in the high-capacity line, allowing lipids to fuel the high metabolism of their hearts for prolonged periods. In contrast, genes important for carbohydrate metabolism and transport were more highly expressed in the unathletic line, similar to what happens in the hearts of humans with heart disease. Expression of genes involved in cell stress and pathological growth signalling was also higher in the low-capacity line, possibly because the hearts of low-capacity runners aren't getting enough oxygen but are constantly pumping blood at a higher pressure.
The results of this study suggest that there is a switch in gene expression between athletes and couch potatoes, from a pattern supporting lipid metabolism and heart muscle contractility to one that indicates an unhealthy heart. The authors have shown that many complex molecular changes contribute to the evolution of athleticism, and have generated novel hypotheses about the links between exercise capacity and heart disease. Although many unanswered questions remain, Bye and colleagues have brought us one step closer to understanding just how much heart it takes to get to the podium!
