Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment
Language: 
English
Short Title: 
Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta
Abstract: 

There is increasing evidence that age-associated chronic low-grade inflammation promotes the development of both large-vessel disease (myocardial infarction, stroke, peripheral arterial disease) and small-vessel pathologies (including vascular cognitive impairment) in older persons. However, the source of age-related chronic vascular inflammation remains unclear. To test the hypothesis that cell-autonomous mechanisms contribute to the proinflammatory changes in vascular phenotype that accompanies advancing age, we analyzed the cytokine secretion profile of primary vascular smooth muscle cells (VSMCs) derived from young (∼13 years old) and aged (∼21 years old) Macaca mulatta. Aged VSMCs cultured in the absence of systemic factors exhibited significantly increased secretion of interleukin-1β, MCP-1, and tumor necrosis factorα compared with young control cells. Secretion of interleukin-6 also tended to increase in aged VSMCs. This age-associated proinflammatory shift in the cellular secretory phenotype was associated with an increased mitochondrial O(2)(-) production and nuclear factor κ-light-chain-enhancer of activated B cells activation. Treatment of aged VSMCs with a physiologically relevant concentration of resveratrol (1 μM) exerted significant anti-inflammatory effects, reversing aging-induced alterations in the cellular cytokine secretion profile and inhibiting nuclear factor κ-light-chain-enhancer of activated B cells. Resveratrol also attenuated mitochondrial O(2)(-) production and upregulated the transcriptional activity of Nrf2 in aged VSMCs. Thus, in non-human primates, cell-autonomous activation of nuclear factor κ-light-chain-enhancer of activated B cells and expression of an inflammatory secretome likely contribute to vascular inflammation in aging. Resveratrol treatment prevents the proinflammatory properties of the aged VSMC secretome, an effect that likely contributes to the demonstrated vasoprotective action of resveratrol in animal models of aging.

Author(s): 
Csiszar, Anna
Sosnowska, Danuta
Wang, Mingyi
Lakatta, Edward G.
Sonntag, William E.
Ungvari, Zoltan
Item Type: 
Journal Article
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Journal Abbreviation: 
J. Gerontol. A Biol. Sci. Med. Sci.
Publication Date: 
Aug 2012
Publication Year: 
2012
Pages: 
811-820
Volume: 
67
Issue: 
8
ISSN: 
1758-535X
DOI: 
10.1093/gerona/glr228
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22219513 PMCID: PMC3536544

Turabian/Chicago Citation

Anna Csiszar, Danuta Sosnowska, Mingyi Wang, Edward G. Lakatta, William E. Sonntag and Zoltan Ungvari. Aug 2012. "Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment." The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 67: 8: 811-820. 10.1093/gerona/glr228.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/gerona/glr228 | issn = 1758-535X | volume = 67 | pages = 811-820 | last = Csiszar | first = Anna | coauthors = Sosnowska, Danuta, Wang, Mingyi, Lakatta, Edward G., Sonntag, William E., Ungvari, Zoltan | title = Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | date = Aug 2012 | pmid = | pmc = }} </ref>