Professor Tara Haas and colleagues in York’s Muscle Health Research Centre studied stimuli that can cause blood vessels in muscle to grow. Their research aims to improve outcomes for patients with peripheral artery disease, a condition that compromises circulation, often seen in patients with high blood pressure or Type 2 diabetes. In the worst-case scenario, lack of blood flow can eventually result in amputation of a patient’s foot or lower leg.

“Type 2 diabetes is one of the major disease states in which muscles don’t get enough blood. This leads to muscle cramps and pain. It becomes a vicious cycle because patients are in so much pain, they can’t do the exercises that would help improve their condition,” says Haas, Associate Professor in York’s School of Kinesiology & Health Science, Faculty of Health. “Ultimately, this research furthers our understanding of how we can jump-start the growth of new vessels, and may lead to drug treatment regimens that will help patients get back on their feet,” she says.

Blood flow itself can be used as a regulator for inducing the growth of new vessels. This process, known as “shear stress-induced angiogenesis,” is not fully understood by scientists.

Eric Gee, PhD candidate in Kinesiology & Health Science and lead investigator on the study, found that increased blood flow jump-starts endothelial growth receptors within the vascular system, in turn causing the activation of a key protein enzyme, p38 MAPK (mitogen-activated protein kinase).

“Experiments suggest that p38 activation is needed to induce the growth of new blood vessels via shear stress-induced angiogenesis,” says Gee.

As part of the study, Gee mimicked the effects of blood flow by pumping fluid over the surfaces of endothelial cells in order to document changes in p38 activation. He also used a drug, Prazosin in an experiment involving rats; the drug dilates arteries and induces chronically-elevated capillary shear stress in skeletal muscle. The rats were then given an inhibitor to block the protein identified in cultured cells. Gee found that the inhibitor worked, suggesting that the p38 protein is important in conveying the signals which stimulate the growth of vessels.

“By learning which healthy pathways are normally activated, we are furthering our knowledge of how to replicate this response in humans,” Gee says. “It also gives us an idea of markers we can look for in disease states where these signals may not be getting activated, for example, high blood pressure, or Type 2 diabetes,” he says.

The article, “p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress-induced angiogenesis,” was published online in the Journal of Cellular Physiology in September 2009. It will appear in print in January 2010.

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Media Contact:

Melissa Hughes, Media Relations, York University, 416 736 2100 x22097 / mehughes@yorku.ca