Cold feet-those chilly appendages that plague many people in the winter and an unlucky few all year round-can be the bane of existence for singles and couples alike. In a new study, scientists led by Selvi C. Jeyaraj of the Research Institute at Nationwide Children's Hospital have identified a biological mechanism that may be responsible for icy extremities: an interaction between a series of molecules and receptors on smooth muscle cells that line the skin's tiny blood vessels. The new research, along with an accompanying editorial by Martin C. Michel of Johannes Gutenberg University in Mainz, Germany, and Paul A. Insel of the University of California at San Diego, suggest new contributors to this near-universal problem and potential targets to treat more serious problems that affect blood vessels in the cold, such as in Raynaud's disease.
The article, entitled "Cyclic AMP-Rap1A Signaling Activates RhoA to Induce a2C-Adrenoceptor Translocation to the Cell Surface of Microvascular Smooth Muscle Cells" (http://bit.ly/N8ZzKh), appears in the Articles in PresS section of the American Journal of Physiology - Cell Physiology (http://ajpcell.physiology.org/) published by the American Physiological Society. The accompanying editorial, "Can You Blame Cold Feet on Epac (and Rap1A)? Focus on "Cyclic AMP-Rap1A Signaling Activates RhoA to Induce α2C-adrenoceptor Translocation to the Cell Surface of Microvascular Smooth Muscle Cells," is also online (http://bit.ly/LYDXFd).
Jeyaraj and her colleagues studied smooth muscle cells derived from tiny blood vessels harvested from human skin biopsies and similar cells from mouse tail arteries. These cells contain receptors known as a2C-AR, which cause constriction in their associated blood vessels and shut off blood flow under chilly conditions to conserve heat. The scientists also worked with different cells, called HEK cells, that do not normally express a2C-AR but that can be modified to do so. Also studied were cells taken from tail arteries of mice genetically altered to no longer express a protein called Rap1A, which the authors hypothesized would interact with a2C-AR.