SCUBE2, vascular endothelium, and vascular complications: A systematic review

•Membrane anchored protein, SCUBE2 expressed in highly vascularized tissues.•SCUBE2 expression linked to Hedgehog (Hh) signaling pathway.•Increased expression of SCUBE2 linked to vascular endothelium dysfunction.•SCUBE2 gene might play a role in vascular inflammation and vascular diseases. The vascular endothelium plays a vital role in regulating normal vascular function. Endothelial lining maintains the balance of thrombolytic and fibrinolytic microenvironment in the vasculature. Alterations of vascular endothelium referred to as endothelial dysfunction, caused the pathological changes in vessel wall such activation of proinflammatory and procoagulatory that initiate atherosclerosis. The concept that endothelial dysfunction plays a critical role in the initiation of atherosclerosis due to vascular inflammation gained tremendous attention. Diabetes mellitus is a metabolic-related disease that caused high mortality and morbidity, leading to its cardiovascular complication over the past decade. Atherosclerosis is the leading cardiovascular complication in diabetes mellitus. Despite metabolic and glycemic control, atherosclerotic plaque progression remains an enormous problem in diabetes mellitus complications. Thus, new inroads therapeutic approach in preventing complications that induced inflammation in endothelial cells could help prevent the disease progression. Signal peptide-CUB-EGF like domain-containing protein 2 (SCUBE2) expressed in vascular endothelium and reported to involve in inflammation. A recent study reported an increased SCUBE2 expression in diabetes mellitus and correlated with high expression of endothelin-1 (ET-1), a proinflammatory endothelial cell-derived peptide. Moreover, this gene showed to increase during atherosclerosis development. The present systematic review will summarize the involvement of SCUBE2 in vascular endothelium function changes and vascular complication, particularly in diabetes mellitus and atherosclerosis.