Chronic high-levels of the stress hormone cortisol could inhibit the growth of blood vessels and lead to cardiovascular complications, as well as poor skeletal muscle blood flow, in people with diabetes, obesity or Cushing’s syndrome, a new study by York researchers has found.
The study by principal researcher Tara Haas of York’s School of Kinesiology & Health Science and Muscle Health Research Centre in the Faculty of Health in collaboration with York kinesiology Professor Michael Riddell was published online in the peer-reviewed journal PLoS One in October.
Tara Haas
“Cortisol is a steroid hormone normally present in our body in small amounts, but a continuous increase in cortisol levels is linked with the development of obesity and Type 2 diabetes,” says Haas. The research by her team looked at the effects of sustained increases in the levels of the stress hormone corticosterone (the form of cortisol found in rodents) on the smallest blood vessels, capillaries, within skeletal muscles.
What they found, says Haas, “was a substantial reduction, by 30 per cent, in the number of capillaries within the muscle.” As capillaries bring oxygen and nutrients to the muscle cells, this reduction could have significant consequences for muscle function and perhaps even blood sugar disposal.
“This is important as a reduction in the number of capillaries could influence the ability of a person to be active, which could cause their condition to worsen,” says Haas. The finding may help to explain why people with Type 2 diabetes have difficulty growing new capillaries in other tissues, such as the heart.
Michael Riddell
The researchers then took a closer look at the mechanisms involved in the reduced capillary growth by using cultured endothelial cells – those cells that form capillaries – chronically treated with the stress hormone. They found that corticosterone repressed several major intracellular signal pathways involved in controlling cell proliferation and migration, which likely contributes to the lack of capillary growth.
“This research is significant because it highlights that a chronic elevation of stress hormone can have significant negative consequences to the small blood vessels within skeletal muscle that are in charge of providing much needed oxygen and nutrients,” says Haas. “It also points the way to identifying how cortisol, through its effects on blocking appropriate blood vessel growth, may contribute to cardiovascular complications of diabetes or obesity.”
Skeletal muscle endothelial cells in culture
Haas says the findings warrant further research to determine if treatment with synthetic steroid hormones carries similar risks. The capillaries in the skeletal muscles studied were affected using a low, but continuous exposure, to the stress hormone. The amount of synthetic steroid hormones, such as hydrocortisone, people are usually prescribed to block inflammation in the body, can be 25 times higher than the amount used in the study.
Haas is a member of the newly formed Angiogenesis Research Group, which investigates the adaptation of the skeletal muscle capillary network to physiological and pathological conditions. The research was supported by the Natural Sciences & Engineering Research Council of Canada (NSERC) Discovery Grants to Haas and Riddell, as well as awards to York students, including Eric A. Shikatani, who was the recipient of a Heart & Stroke Foundation of Ontario Master’s Studentship Award. In addition, student Anastassia Trifonova was the recipient of a NSERC CGSM graduate scholarship, and Anna Krylova and Andrei Szigiato were recipients of NSERC Undergraduate Student Research awards.
By Sandra McLean, YFile deputy editor