Cardiovascular diseases are the number one cause of death in the western world. Endothelial cells that line the blood vessels of the heart play a central role in the development of these diseases. In addition to helping transport blood, these cells support the normal running of the heart, and help it to grow and regenerate. Over time as the body ages and experiences stress, endothelial cells start to deteriorate. This can cause the cells to undergo senescence and stop dividing, and lay down scar-like tissue via a process called fibrosis. As a result, the blood vessels start to stiffen and become less susceptible to repair.
Ageing, obesity, high blood pressure, and inactivity all increase the risk of developing cardiovascular diseases, whereas regular exercise has a protective effect. But it was unclear how these different factors affect endothelial cells. To investigate this, Hemanthakumar et al. compared the gene activity of different sets of mice: old vs young, obese vs lean, heart problems vs healthy, and fit vs sedentary.
All these risk factors – age, weight, inactivity and heart defects – caused the mice’s endothelial cells to activate mechanisms that lead to stress, senescence and fibrosis. Whereas exercise training had the opposite effect, and turned off the same genes and pathways. All of the at-risk groups also had high levels of a gene called SerpinH1, which helps produce tissue fiber and collagen. Experiments increasing the levels of SerpinH1 in human endothelial cells grown in the laboratory recreated the effects seen in mice, and switched on markers of stress, senescence and fibrosis.
According to the World Health Organization, cardiovascular disease now accounts for 10% of the disease burden worldwide. Revealing the affects it has on gene activity could help identify new targets for drug development, such as SerpinH1. Understanding the molecular effects of exercise on blood vessels could also aid in the design of treatments that mimic exercise. This could help people who are unable to follow training programs to reduce their risk of cardiovascular disease.