TLR signaling: an emerging bridge from innate immunity to atherogenesis.
Chronic inflammation and disordered lipid metabolism represent hallmarks of atherosclerosis. Considerable evidence suggests that innate immune defense mechanisms might interact with proinflammatory pathways and contribute to development of arterial plaques. The preponderance of such evidence has been indirect clinical and epidemiologic studies, with some support from experimental animal models of atherosclerosis. However, recent data now directly implicate signaling by TLR4 in the pathogenesis of atherosclerosis, establishing a key link between atherosclerosis and defense against both foreign pathogens and endogenously generated inflammatory ligands. In this study, we briefly review these and closely related studies, highlighting areas that should provide fertile ground for future studies aimed at a more comprehensive understanding of the interplay between innate immune defense mechanisms, atherosclerosis, and related vascular disorders.
Michelsen
Kathrin S
KS
Division of Pediatric Infectious Diseases, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California-Los Angeles, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Doherty
Terence M
TM
Shah
Prediman K
PK
Arditi
Moshe
M
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000517:prevention & control; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors