The University of Rochester Medical Centre have been researching an old yet important question.   How do flexing muscles tell nearby blood vessels that they need more blood to perform?  A study published in the Journal "Circulation Research" appears to have some answers.  The findings suggest new ways to reverse poor circulation and heal wounds - both of which are relevant to everyone - but especially to persons with a disability.

The study mechanism suggests new ways to treat conditions that involve poor circulation like peripheral artery disease (PAD), which comes with aging, affects millions around the world and leads to amputation in the worst cases.

PAD also makes a patient four to five times more likely to suffer a heart attack or stroke, according to the American Heart Association. Furthermore, the same signals that influence circulation in some tissues drive cell growth elsewhere, creating promise for improvements in the treatment of chronic wounds.

In the larger picture, the study results reflect the rise of the extracellular matrix (ECM), a network of proteins that surrounds all cells in the body.

Differences in the amounts and types of proteins assembled into the ECM gives rise to various forms of matrix, including both hard connective tissues like bone and the soft connective tissues that surround organs. Once thought to be no more than inert scaffolding that anchors cells and lends shape to human tissue, ECM connective tissue has emerged as a vital signaling partner with cells in controlling bodily function.

The results of the study also reflect a growing recognition of physical force as a driver of biochemical reactions that contribute to both health and disease. Force applied to bone by weightlifting, for example, is now known to thicken bone. The force of fast blood flow on blood vessel walls may protect them from atherosclerosis.

The two trends come together in the new study, which explains for the first time how the force of contracting muscle increases blood flow to that muscle by sending biochemical messages through nearby matrix proteins. Flexing skeletal muscle was found to change the shape of the matrix protein fibronectin, which in turn, signaled for the relaxation of smooth muscle surrounding blood vessels. This enabled the vessels to dilate, increasing blood flow through them. The authors have also shown that a key piece of fibronectin, on its own, causes blood vessels to dilate, a first step toward pro-circulatory drug design.

“Along with a fundamental contribution to the understanding of exercise physiology, our data study suggests that engineering fibronectin could provide a simple, elegant way to maintain normal blood vessel function in the aging, and to restore such function in hard-to-heal wounds,” said Ingrid H. Sarelius, Ph.D., professor of Pharmacology and Physiology at the University of Rochester Medical Center, and a study author. “Aging and disease bring changes in matrix structure, and we may be able to reverse them.”