Alpha4 integrins and vascular cell adhesion molecule-1 play a role in sympathetic innervation of the heart

TitleAlpha4 integrins and vascular cell adhesion molecule-1 play a role in sympathetic innervation of the heart
Publication TypeJournal Article
Year of Publication2002
AuthorsWingerd KL, Goodman NL, Tresser JW, Smail MM, Leu ST, Rohan SJ, Pring JL, Jackson DY, Clegg DO
JournalThe Journal of Neuroscience
Date Published2002 Dec 15
KeywordsAnimals, Antibodies, Cells, Cultured, Chickens, Ganglia, Sympathetic, Heart, Integrin alpha4, Integrin alpha4beta1, Mice, Myocardium, Neurites, Rats, Rats, Long-Evans, Recombinant Proteins, Superior Cervical Ganglion, Vascular Cell Adhesion Molecule-1

Sympathetic neurons innervate the heart early in postnatal development, an event that is crucial for proper modulation of blood pressure and cardiac function. However, the axon guidance cues that direct sympathetic neurons to the heart, and the neuronal receptors that recognize those cues, are poorly understood. Here we present evidence that interactions between the alpha4beta1 integrin on sympathetic neurons and vascular cell adhesion molecule-1 (VCAM-1) in the heart plays a role in cardiac innervation. The alpha4 subunit was detected on postnatal rat superior cervical ganglion (SCG) neurons in culture and in cryosections of SCG and heart. VCAM-1 immunoreactivity was detected on cardiac myocytes that associate with invading sympathetic neurons. Purified recombinant soluble VCAM-1 (rsVCAM-1) stimulated SCG neurite outgrowth at levels comparable with laminin 2/4 and fibronectin (Fn), and outgrowth on rs-VCAM-1 and Fn was blocked by antibodies specific for the alpha4 and beta1 integrin subunits. Intrathoracic injection of function-blocking antibodies to alpha4 and VCAM-1, as well as a small molecule inhibitor of alpha4 integrins, significantly reduced sympathetic innervation of the heart. These results indicate that the interaction between alpha4 integrin and VCAM-1 is important for sympathetic innervation of the heart.

Alternate JournalJ. Neurosci.
PubMed ID12486170
Grant ListEY06916 / EY / NEI NIH HHS / United States