Association of Fetuin-A with Carotid Intima-Media Thickness and Vascular Diseases

Abstract

Fetuin-A, also known as alpha 2-Heremans-Schmid glycoprotein (AHSG), is a member of the cystatin superfamily of cysteine protease inhibitors and has different functions in human physiology and pathophysiology. Most studies suggest a biphasic effect of fetuin-A depending on the stages of atherosclerosis. Serum levels of fetuin-A are decreased in cases of acute inflammation. Therefore, it is known as a negative acute-phase protein. Fetuin-A inhibits insulin signaling and pathological calcification and has emerged as a diabetogenic agent. Fetuin-A levels are also found to be related to visceral obesity and dyslipidemia. Some authors have claimed that fetuin-A has a proatherogenic role, but it is still unclear whether high fetuin-A levels accelerate atherosclerosis except in the case of diabetes mellitus (DM). One of the most important reasons for this uncertainty is the fact that there is a very weak compatibility between fetuin-A measurements performed by two different commercial enzyme-linked immunosorbent assay (ELISA) kits. Because the early sign of atherosclerosis is carotid intima-media thickness (CIMT), attention has been drawn to the relationship between CIMT and fetuin-A, especially in patients with DM. A number of studies in the literature have demonstrated an inverse correlation between fetuin-A and CIMT in patients who had chronic inflammatory disease but not DM. In addition, there is no association between fetuin-A and CIMT in subjects without known clinical cardiovascular disease. However, it seems that high fetuin-A levels accelerate atherosclerosis in DM and that diabetic patients exhibit a positive correlation between fetuin-A and CIMT.