Homeostatic role of Toll-like receptor 4 in the endothelium and heart.
Toll-like receptor 4 (TLR4) is a pattern recognition receptor for lipopolysaccharide from Gram negative bacteria and thus is integral to the innate immune response in mammals. In addition, TLR4 is associated with atherosclerosis in murine models. The current study shows that blood vessels from TLR4(-/-) mice have an intact endothelial layer and comparable expression of nitric oxide synthase 3 protein. However, endothelium-dependent dilation in response to acetylcholine in vessels from TLR4(-/-) mice is greatly reduced. By contrast, endothelium-independent smooth muscle dilation in response to sodium nitroprusside in vessels from TLR4(-/-) mice remains intact. Furthermore, this study shows that hearts from TLR4(-/-) mice display signs of left ventricular dilation. In contrast to results in vessels from TLR4(-/-) mice, endothelium-dependent responses to acetylcholine in vessels from TLR2(-/-) mice remain intact. These observations illustrate a novel role for TLR4 in the homeostatic control of a functional endothelium and, thereby, cardiovascular health.
Harrington
Louise S
LS
Cardiac, Vascular, and Inflammation Research, William Harvey Institute, Queen Mary's University of London, Charterhouse Square, London, EC1M 6BQ. l.harrington@imperial.ac.uk
Belcher
Elizabeth
E
Moreno
Laura
L
Carrier
Martin J
MJ
Mitchell
Jane A
JA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; D051197:Toll-Like Receptor 4; D014665:Vasodilator Agents; D009599:Nitroprusside; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine