Immune effector mechanisms implicated in atherosclerosis: from mice to humans

Abstract

According to the traditional view, atherosclerosis results from a passive buildup of cholesterol in the artery wall. Yet, burgeoning evidence implicates inflammation and immune effector mechanisms in the pathogenesis of this disease. Both innate and adaptive immunity operate during atherogenesis and link many traditional risk factors to altered arterial functions. Inflammatory pathways have become targets in the quest for novel preventive and therapeutic strategies against cardiovascular disease, a growing contributor to morbidity and mortality worldwide. Here we review current experimental and clinical knowledge of the pathogenesis of atherosclerosis through an immunological lens and how host defense mechanisms essential for survival of the species actually contribute to this chronic disease but also present new opportunities for its mitigation.

Figure 1. A Potential Role for Low-Density Lipoprotein as an Antigen that Promotes Atherosclerosis

Native LDL can undergo slight oxidative modification that permits its uptake by PRRs on APCs (which may include DCs) but does not alter amino acid side chains in ApoB sufficiently to interfere with immunogenicity. The ApoB-derived proteins, presented in the context of self MHC, with appropriate costimulation, stimulate proliferation of the antigen-specific T cell clone and aggravation of atherogenesis.