Clinical implications of fetuin-A

Abstract

Fetuin-A, also termed alpha2-Heremans-Schmid glycoprotein, is a 46 kDa hepatocyte derived protein (hepatokine) and serves multifaceted functions. (i) It acts as systemic inhibitor of extraosseous calcification, serves as transport protein for calcium and phosphate in colloidal calciprotein particles and is involved in bone mineralization. Severe derangements of this system occur in chronic renal disease and are associated with mineral bone disorder. Fetuin-A levels have been associated with survival of renal and transplant patients. Low fetuin-A and high calcification propensity each increase mortality. (ii) An independent second aspect of fetuin-A is its interaction with the insulin receptor. Associations of fetuin-A levels with metabolic syndrome as well as pursuant atherosclerotic vascular effects have been established. This could be explained by differences in patient characteristics, different stages of vascular calcifications, presence of diabetes and kidney dysfunction. (iii) A further issue is the acute phase response of fetuin-A to various inflammatory stimuli and injuries. Dependent on the mode of stimulation, fetuin-A may work as a positive or negative acute phase protein. It may also serve as a protective agent in severe systemic inflammation. A suggestive role of fetuin-A may evolve in wasting and malnutrition–inflammation–atherosclerosis syndromes of chronic disease. A novel aspect is the putative role of fetuin-A in adipose tissue inflammation. (iv) With respect to heart disease, aspects of coronary arterial disease, heart failure and valvular stenosis and calcification have been elucidated. Associations of fetuin-A levels have been found with coronary artery disease, ischemic cardiomyopathy and aortic stenosis.