Vascular Odorant Receptors - Regulation & Function

Identifying new approaches to regulate inflammation and cardiovascular disease by understanding the role of odorant receptors

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Full Project Name:Vascular Odorant Receptors - Regulation & FunctionPrincipal Investigator:William Campbell, PhD, Pharmacology and ToxicologyCo-Investigator:David Gutterman, MD, MedicineAward Amount:$200,000

Award Date

January2016

Project Duration:24 months

Project Description Narrative:

More than 67.5 million American adults have hypertension (high blood pressure) and 11.8% are resistant to current therapies. Cardiovascular diseases are a major cause of death, and while survival has improved, treatment failures remain high.

Hypertension, ischemic heart disease, diabetes and heart failure are associated with the vessels' impaired ability to dilate and the presence of inflammation. Because these diseases have vascular and inflammatory components, new approaches to understanding vascular regulation and function are needed to improve treatment and survival. The identification of new odorant receptors (ORs) has led to new knowledge in the areas of vascular biology, inflammation and cardiovascular disease.

Through this award, investigators aim to gain understanding of this pathway to advance understanding of vascular regulation and inflammation, and identify new approaches to regulate inflammation and cardiovascular disease.

Outcomes & Lessons Learned:

Continued to build from team's discovery that the Ms4a family of proteins is expressed in high levels in vascular cells. These proteins are found in nasal tissue and known to sense some odorant. These proteins differ from typical odorant receptors in their structure, and their effects are due to calcium entry into cells. This is a significant and novel finding that suggests an important, unrecognized role for these proteins in vascular biology. This discovery exceeded the research team's expectations for the initiative and poses an exciting new changemaking direction to the research
Learned that human vascular cells express specific odorant receptors as well as the proteins of the intracellular pathway mediating the effects of odorants. These receptors and proteins are found in smooth muscle cells that regulate dilation and constriction of arteries. While more evidence is needed, these studies support the possibility that odorants regulate the blood flow to organs and blood pressure by dilating or constricting arteries