Shunguang Wei, PhD, Research Assistant Professor in Cardiovascular Medicine, has been awarded a five-year, $1.91 million grant from the National Heart, Lung, and Blood Institute (NHLBI) to study a novel treatment of sympathetic excitation in heart failure. The R01 will allow Dr. Wei to further his research into the central neural mechanisms underlying heart failure.
Tumor necrosis factor alpha (TNF-α) is a cytokine implicated in the pathophysiology of heart failure. This cell signaling protein increases in cardiovascular/autonomic-related regions of the brain in a rat model of heart failure. It also contributes to the activation of chemicals in neurons in that setting. Unlike other cytokines, TNF-α is initially produced as a transmembrane protein. TACE, a TNF-α converting enzyme, cleaves to the transmembrane protein to release its mature form, the soluble TNF-α, which mediates inflammatory and immune responses. TACE is also upregulated in cardiovascular/autonomic centers of the brain and can alter cardiovascular function and sympathetic drive in animal models of heart failure.
Dr. Wei’s project will explore this previously unrecognized role of brain TACE in TNF-α-induced central inflammatory mechanisms and how they drive sympathetic nerve activity in heart failure, thus identifying a novel anti-TNF target for pharmacological intervention.