The Cardiovascular Risk Prognostication in Diabetes Mellitus: The Role of Myeloid-related Protein Complex Calprotectin

Abstract

The low-intense inflammation is discussed as a one of the clue of various faces of pathogenesis of diabetes mellitus (DM) including insulin resistance, mitochondrial dysfunction, lipotoxity, oxidation injury that contributed in cardiovascular (CV) disease and clinical outcomes. However, there are a lot of candidates for on early biological marker that could stratify DM patients at CV risk. The myeloid-related protein 8/14 known as calprotectin is a heterodimeric complex of calcium-binding proteins, which is predominantly expressed in activated human neutrophils, monocytes, adipocytes, and innate immunity cells including macrophages, but not in normal tissue macrophages. Calprotectin may activate of Toll-like receptor 4 as innate amplifier of infection, autoimmunity, and cancer that attenuates some extracellular functions, i.e. antimicrobial, cytostatic, and chemotactic activities. Therefore, calprotectin activates of NADPH oxidase, induces apoptotic caspase-9 and caspase-3 activation, DNA fragmentation, and membrane phosphatidylserine exposure, and increases the activation of nuclear factor-κB by promoting the nuclear translocation of p65 in target cells. Recent clinical studies have shown that calprotectin was found as a marker for activation of granulocytes, mononuclear phagocytes and immune cells that play a pivotal role in tissue damage, it could link important molecular pathological mechanisms of inflammation contributing to endothelial damage. The aim of the review is summarize of knowledge regarding predictive value of calprotectin as surrogate biomarker of CV events in DM patients.