Role of integrins in cardiac innervation and function

Smoking is known to be a high risk factor in heart disease. Smoking may contribute to heart disease via long term stimulation of the sympathetic innervation of heart muscle and blood vessels. Thus, it may be beneficial to use drugs to decrease the sympathetic innervation of the heart to treat hypertension. However, the molecular interactions that underlie the in growth of axons into heart tissue during development, and the factors that maintain the innervation of the heart are not understood. It is thought that receptor proteins on the surface of sympathetic neuronal cells recognize proteins on heart cell surfaces and this leads to extension of axons into the heart. These same interactions may result in maintenance of the innervation in the adult.

We have obtained preliminary evidence suggesting that an alpha4 integrin receptor on sympathetic neurons interacts with Vascular Cell Adhesion Molecule-1 (VCAM-1) on heart cells to guide axons into the heart during development. Experiments are proposed to test this hypothesis. If we can show that the interaction between these two proteins is important in establishing the innervation of the heart, it may be possible to treat hypertension and other types of heart disease with drugs that block the interaction between alpha4 integrin. and VCAM-1. Such treatments would result in a decrease in sympathetic innervation and therefore less norepinephrine would be released. Thus, strategies might be developed to treat heart disease associated with smoking.