Neuregulin-4, an Adipokine, as a Residual Risk Factor of Atherosclerotic Coronary Artery Disease

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

“…In fact, treatment with Nrg1, which can also activate ErbB4, alleviated neointima formation following vascular injury and inhibited the proliferation of vascular smooth muscle cells. Signalling through ErbB4 tyrosine kinase receptors exhibits an antiapoptotic effect by stimulating the Akt/PI3K pathway, which has been reported to prevent endothelial cell apoptosis and thereby reduce the progression of atherosclerosis . However, these indirect results are not decisive.…”

“…Recent studies suggest that ErbB4 gene polymorphisms are linked to obesity, type 2 diabetes mellitus (T2DM), and diabetic nephropathy, suggesting a major role of Nrg4/ErbB4 signalling in the development of metabolic complications . Although Nrg4, an ErbB4‐specific ligand, is expressed in different organs and was first identified as a neuregulin family protein enriched in the pancreas, subsequent studies revealed that brown adipose tissue (BAT) expresses the highest levels of Nrg4 . Nrg4, a recently identified adipokine, is a member of the epidermal growth factor (EGF) family of extracellular protein ligands that functions in an autocrine/paracrine or endocrine manner via a proteolytic liberation of the EGF‐like domain .…”

Newly Discovered Adipokines: Pathophysiological Link Between Obesity and Cardiometabolic Disorders

“…In addition, NRG4 and coronary artery disease (CAD) have a negative association ( Tian et al, 2019 ). The underlying physiology of the relationship between NRG4 and CAD is not fully studied; NRG4 has an anti-apoptotic effect on endothelial cells and prevents the development of atherosclerosis ( Sato and Minatsuki, 2019 ).…”

The Etiology of Adnexal Masses in Women with a History of Non-Gynaecologic Malignancy: Recurrence, Second Primary or None?

“…In vivo studies have suggested that NRG-4 levels change during the process of lipogenesis, inflammatory events and as a result of changes in energy metabolism ( 10 , 11 ). It has been suggested that NRG-4 positively correlates with the development of obesity related disorders, such as type 2 diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD) and plays a role in the development of coronary artery disease (CAD) by promoting atherosclerosis ( 12 , 13 , 14 , 15 , 16 , 17 ).…”