Interleukin-17 and Atherosclerotic Vascular Disease

Atherosclerotic vascular disease (ASVD) involves several overlapping pathological processes. Atherogenesis, the process by which atherosclerotic plaques develop in the arterial wall, involves inspissation of abnormal circulating lipoproteins into the vessel intima, resulting in inflammation, injury, and responses to injury.1 Mouse models of atherogenesis, involving impaired low-density lipoprotein clearance due to gene knockout of either apolipoprotein E (ApoE) or low-density lipoprotein receptor, are widely used to study this process. The presence of plaques in humans sets the stage for complications, such as plaque rupture or fissure that stimulate thrombosis; intraplaque hemorrhages that may rapidly cause luminal impingement; more gradual but progressive vascular stenoses due to inadequate outward remodeling that produce chronic ischemia; inflammatory aneurysms with the potential for catastrophic events, such as aortic rupture; or plaque embolization, leading to infarcts in tissues distal to the plaque site. Each of these complications arises from distinct but overlapping causes, of which inflammation is a significant component.2 Mouse models for the study of these complications have significant limitations.See accompanying article on page 1565Inflammation in ASVD is best described as chronic active, involving acute exacerbations superimposed on a more persistent, indolent process. The initial trigger for inflammation in the vessel wall may be innate immunity, an inflammatory process that is activated by myeloid cells or some types of innate lymphocytes recognizing conserved motifs in microbe-derived molecules or of endogenous molecules that are released as a consequence of cell injury. Recognition …