IJCS | Volume 31, Nº5, September / October 2018

533 Figure 1 - Pathological mechanisms triggered by neutrophils and lymphocytes during the evolution of cardiovascular diseases. As the neutrophil / lymphocyte ratio increases, there is an association with the pathophysiological mechanism of endothelial dysfunction. Pro-inflammatory factors are derived from increased numbers of neutrophils (green frame), while the attenuation of anti-inflammatory factors is the result of decreased lymphocytes. ROS: reactive oxygen species; MPO: myeloperoxidase; ICAM-1: intercellular adhesion molecule-1. Source: Santos e Izidoro. Endothelial dysfunction ROS MPO ICAM-1 Elastase Platelet aggregation Macrophages Chemokines Decrease of anti- inflammatory factors Lymphocyte Neutrophil Santos & Izidoro NLR in CVD risk assessment Int J Cardiovasc Sci. 2018;31(5)532-537 Review Article especially in atherosclerosis. Neutrophils are related, since the initial phase, to a more advanced stage of atherosclerosis, participating in the inflammatory process as a hyperlipidemia mediator, until the development of atherothrombosis, infiltrating the atherosclerotic arteries. 11 In such pathophysiological circumstances, it seems that the increase in neutrophils is associated with the maturation stage of these cells, exhibiting nuclear segmentation. 10,12-15 Therefore, it is more likely that the predominant neutrophilia originates from the segmented cell type, since atherosclerosis is a chronic inflammatory condition, 16,17 as well as the process of thrombosis. 18,19 The neutrophils activate the macrophages, acquiring the lipidmediation function. Subsequently, macrophages express atherogenic factors, such as interleukin-6 (IL-6), CD40 and CD80, in addition to being susceptible to foam cell formation. 7,8,20-25 The neutrophil cells, themselves, also express atherogenic factors, such as chemokines and cytokines. 11 When myocardial tissue damage occurs, leading to inflammation, neutrophils are highlighted, releasing arachidonic acid metabolites, chemokines, reactive oxygen species (ROS), intercellular adhesionmolecules-1 (ICAM-1), platelet factors and several enzymes, such as myeloperoxidase (MPO) and elastase, facilitating the rupture of the atherosclerotic plaque by weakening the fibrotic layer, and thematrix ends up being degraded. 3,11,26 MPO, an enzyme abundantly expressed in primary neutrophil granulocytes, is one of the most impacting components of endothelial dysfunction, as it limits nitric oxide and, through its catalytic activity, promotes the formation of oxidized low-density lipoprotein (LDL). Thus, subsequently, macrophages phagocyte the oxidized LDL, forming the foam cells. 11 Pathologicalmechanismsoriginatingfromneutrophils and lymphocytes during cardiovascular diseases Epidemiological evidence has shown the predictive role of NLR in atherosclerotic manifestations. 27-30 The states of lymphopenia disclosed by thewhole blood count are associated with atherosclerosis progression, and the decrease in lymphocytes may be caused by apoptotic