Aging enhances the basal production of IL-6 and CCL2 in vascular smooth muscle cells.
OBJECTIVE
Increased circulating cytokine levels are a prominent feature of aging that may contribute to atherosclerosis. However, the role vascular cells play in chronic inflammation induced by aging is not clear. Here, we examined the role of aging on inflammatory responses of vascular cells.


RESULTS
In an ex vivo culture system, we examined the inflammatory response of aortas from young (2-4 months) and aged (16-18 months) mice under nonstimulatory conditions. We found that basal levels of interleukin-6 were increased in aged aortas. Aged aortic vascular smooth muscle cells (VSMC) exhibited a higher basal secretion of interleukin-6 than young VSMC. Gene and protein expression analysis revealed that aged VSMC exhibited upregulation of chemokines (eg, CCL2), adhesion molecules (eg, intracellular adhesion molecule 1), and innate immune receptors (eg, Toll-like receptor [TLR] 4), which all contribute to atherosclerosis. Using VSMC from aged TL4(-/-) and Myd88(-/-) mice, we demonstrate that signaling via TLR4 and its signal adaptor, MyD88, are in part responsible for the age-elevated basal interleukin-6 response.


CONCLUSIONS
Aging induces a proinflammatory phenotype in VSMC due in part to increased signaling of TLR4 and MyD88. Our results provide a potential explanation as to why aging leads to chronic inflammation and enhanced atherosclerosis.
Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
Yang
Y
Song
Hua
H
Shen
Dominik
D
Schenten
Peiying
P
Shan
Patty J
PJ
Lee
Daniel R
DR
Goldstein
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000276:immunology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics; D015854:Up-Regulation
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4