Neuregulin as a heart failure therapy and mediator of reverse remodeling.
The beta isoform of Neuregulin-1 (NRG-1β), along with its receptors (ErbB2-4), is required for cardiac development. NRG-1β, as well as the ErbB2 and ErbB4 receptors, is also essential for maintenance of adult heart function. These observations have led to its evaluation as a therapeutic for heart failure. Animal studies and ongoing clinical trials have demonstrated beneficial effects of two forms of recombinant NRG-1β on cardiac function. In addition to the possible role for recombinant NRG-1βs as heart failure therapies, endogenous NRG-1β/ErbB signaling appears to play a role in restoring cardiac function after injury. The potential mechanisms by which NRG-1β may act as both a therapy and a mediator of reverse remodeling remain incompletely understood. In addition to direct effects on cardiac myocytes NRG-1β acts on the vasculature, interstitium, cardiac fibroblasts, and hematopoietic and immune cells, which, collectively, may contribute to NRG-1β's role in maintaining cardiac structure and function, as well as mediating reverse remodeling.
Cristi L
CL
Galindo
Sergey
S
Ryzhov
Douglas B
DB
Sawyer
D015415:Biomarkers / Q000097:blood; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000175:diagnosis; D066246:ErbB Receptors / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D020890:Neuregulin-1 / Q000097:blood / Q000502:physiology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
D015415:Biomarkers; D002317:Cardiovascular Agents; C094131:NRG1 protein, human; D020890:Neuregulin-1; D011994:Recombinant Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors