Aging enhances the basal production of IL-6 and CCL2 in vascular smooth muscle cells.

Journal Article (Journal Article)

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. METHODS AND 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.

Full Text

Duke Authors

Cited Authors

  • Song, Y; Shen, H; Schenten, D; Shan, P; Lee, PJ; Goldstein, DR

Published Date

  • January 2012

Published In

Volume / Issue

  • 32 / 1

Start / End Page

  • 103 - 109

PubMed ID

  • 22034510

Pubmed Central ID

  • PMC3241880

Electronic International Standard Serial Number (EISSN)

  • 1524-4636

Digital Object Identifier (DOI)

  • 10.1161/ATVBAHA.111.236349

Language

  • eng

Conference Location

  • United States