Circulating neuregulin-1β levels vary according to the angiographic severity of coronary artery disease and ischemia

Abstract

Background Coronary artery disease (CAD) is the leading killer in the U.S. Patients with severe CAD and ischemia have worse prognosis. Therefore expansion of biomarker research, to identify at risk individuals and explain the complex biology between cardiovascular growth factors and atherosclerosis is needed. Neuregulin-1β (NRG-1β) is a myocardial stress activated growth and survival factor released from endocardial and endothelial cells. NRG-1β is essential for cardiovascular development and a regulator of angiogenesis. We postulated that plasma and serum levels of NRG-1β would vary in relation to CAD severity and the presence of stress-induced ischemia. Methods We measured serum and plasma levels of NRG-1β and vascular endothelial growth factor (VEGF) in 60 patients undergoing cardiac catheterization. CAD severity was calculated from angiographic results using a modified Duke jeopardy score. Results Serum NRG-1β (sNRG-1β), plasma NRG-1β (pNRG-1β), serum VEGF (sVEGF), and plasma VEGF (pVEGF) were detectable in the majority of patients. The pNRG-1β levels were approximately two fold higher than sNRG-1β. Both sNRG-1β and pNRG-1β correlated inversely with CAD severity. Plasma NRG-1β levels were statistically higher in patients with stress-induced ischemia denoted by a positive myocardial perfusion imaging study that correlated with angiographic findings (p = 0.02). Conclusions Both serum and plasma NRG-1β correlated inversely with angiographic severity of CAD. Plasma NRG-1β levels were two fold higher than serum and were higher in patients with stress-induced ischemia. Therefore we conclude that plasma is the optimal source for the further exploration of the biological significance of NRG-1β as a biomarker of CAD severity and ischemia.

Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors

“…Ky et al reported that circulating NRG-1 levels are increased in chronic heart failure of ischemic but not of non-ischemic etiology (16). Geisberg et al reported plasma NRG-1β levels were statistically higher in patients with stress-induced ischemia, and NRG-1β levels were inversely correlated with ischemia severity (17). These findings suggest that ischemia may be an important trigger for endothelial NRG-1 synthesis and release.…”

Neuregulin in Cardiovascular Development and Disease

“…92 In patients with stable coronary disease without ischemia or heart failure, NRG-1β levels were inversely associated with coronary arterial disease severity. 93 Interestingly, NRG-1β levels were higher in patients with stress-induced ischemia. These results are consistent with the concept that myocardial NRG-1β is activated in response to ischemia as observed in the isolated heart.…”

Neuregulin as a Heart Failure Therapy and Mediator of Reverse Remodeling

“…higher NRG-1β levels in in class II and IV, compared to class I or II) (49). A subsequent study likewise found higher levels of NRG-1β in both plasma and serum of patients with coronary artery disease (CAD) who exhibited stress-induced ischemia (50). However, circulating levels of NRG-1β in stable CAD patients were found to be inversely correlated with angiographic severity of disease (50).…”