Recent Advances in the Role of Immunity in Atherosclerosis

Abstract

The immune system serves to protect the host from a diverse array of pathogens that evolve rapidly in an effort to breach immune security checkpoints. These defense mechanisms operate continuously to keep exogenous pathogens from propagating their own species, although this heightened security has unintended and detrimental consequences to the host.1 Although this maladaptive immune response is classically associated with noninfectious diseases, such as arthritis, gout, and lupus, uncontrolled inflammation is emerging as a causative factor in the development of cardiovascular disease as well. Atherosclerosis is a widely known condition in which the immune system causes harm to the host. Classically defined as a disease that is initiated by alterations in cholesterol metabolism and the subendothelial retention of low-density lipoproteins (LDL),2 we now know that activation of both innate and adaptive immunity participate in atherogenesis.3 Advanced atherosclerotic plaques are characterized by highly inflammatory lesions that can both impede blood flow and precipitate thrombosis because of plaque rupture, leading ultimately to the clinical manifestations of atherosclerosis: myocardial infarction, and stroke. The progression of atherosclerosis in humans is associated with increased circulating levels of proinflammatory C-reactive protein, as well as increased white blood cell count.3,4 A considerable amount of evidence implicates the innate immune system in the progression of atherosclerosis.5 Recent studies suggest that polymorphonuclear neutrophils (PMNs) drive the accumulation of monocytes in atherosclerotic lesions in a manner dependent on PMN granule proteins, such as the cathelicidins (ie, cathelicidin-related antimicrobial peptide).6–9 Other comorbidities, such as hyperglycemia, also contribute to the mobilization of PMNs from the bone marrow during atherosclerosis progression.10 Interestingly, the PMN/lymphocyte ratio may have value in predicting future cardiovascular events over the white blood cell count alone.11 Although the role of PMNs in atherogenesis is emerging, the roles …