Atherosclerosis and innate immune signaling

Abstract

Atherosclerosis, the leading cause of death in developed countries, is characterized by chronic inflammation in the artery wall. It has been appreciated for decades that this disease is linked to hypercholesterolemia and the accumulation of macrophages in the artery wall, yet the exact mechanisms underlying this inflammatory process remain unclear. The role of innate and adaptive immune responses in the pathogenesis of atherosclerosis has been an area of intense study. It now appears that activation of innate immune signaling pathways designed to protect us from microbes may be responsible for initiating and feeding the chronic inflammatory cascade that characterizes this disease. In this review, we discuss the recent identification of Toll-like receptors and their downstream signaling pathways as critical contributors to atherosclerosis. Unraveling the contribution of individual Toll-like receptors and identifying the ligands that activate these pathways will be a central focus of atherosclerosis research in the next few years. The involvement of these pathways in atherogenesis will not only open up new avenues of investigation, but it also provides new targets for therapeutic manipulation that could ameliorate the atherosclerotic inflammatory response directly.

Fungal pathogen recognition by scavenger receptors in nematodes and mammals

“…1 In addition, the inappropriate activation of these receptors by endogenous self ligands can contribute to chronic inflammatory syndromes and autoimmunity. [2][3][4] Several families of PRRs have been described, including the Toll-like receptors (TLRs), C-type-lectins, NOD-like receptors (NLRs), and RNA helicases. 1,[5][6][7] Another class of PRRs are the scavenger receptor (SRs) family of proteins (Fig.…”

Inactivity and Inflammation in the Critically Ill Patient

“…Antioxidants are reduced during disease states common to ICU patients such as COPD, acute lung injury, atherosclerosis, and acute renal failure [43,56,57]. These antioxidants are produced by skeletal muscles [53].…”

A Microbial TLR2 Agonist Imparts Macrophage-Activating Ability to Apolipoprotein A-1

“…Experimental models using these organisms, such as P. gingivalis (39), show that they can indeed induce atherosclerotic inflammation, although the mechanism(s) by which they might promote this disease is not clear. It has been proposed recently that innate recognition by TLR2 in conjunction with either TLR1 or TLR6 of a wide range of microbial agonists is a potential inflammatory pathway whereby microbial moieties might be involved (17,40). In fact, Mullick et al (19) recently demonstrated that the systemic administration of the synthetic TLR2-using Pam 3 CSK 4 lipopeptide could greatly enhance atherosclerosis in a mouse model using the LDL receptor KO Ϫ/Ϫ mouse, and that disease was ablated when TLR2 was eliminated through use of Ldl Ϫ/Ϫ , TLR2 Ϫ/Ϫ mice.…”