Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-κB and PPAR signaling

Huiyun Shen, Elizabeth Oesterling, Arnold Stromberg, Michal Toborek, Ruth MacDonald, Michal J Toborek

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Objectives: Marginal intake of dietary zinc can be associated with increased risk of cardiovascular diseases. In the current study we hypothesized that vascular dysfunction and associated inflammatory events are activated during a zinc deficient state. Design: We tested this hypothesis using both vascular endothelial cells and mice lacking the functional LDL-receptor gene. Results: Zinc deficiency increased oxidative stress and NF-κB DNA binding activity, and induced COX-2 and E-selectin gene expression, as well as monocyte adhesion in cultured endothelial cells. The NF-κB inhibitor CAPE significantly reduced the zinc deficiency-induced COX-2 expression, suggesting regulation through NF-κB signaling. PPAR can inhibit NF-κB signaling, and our previous data have shown that PPAR transactivation activity requires adequate zinc. Zinc deficiency down-regulated PPARα expression in cultured endothelial cells. Furthermore, the PPARγ agonist rosiglitazone was unable to inhibit the adhesion of monocytes to endothelial cells during zinc deficiency, an event which could be reversed by zinc supplementation. Our in vivo data support the importance of PPAR dysregulation during zinc deficiency. For example, rosiglitazone induced inflammatory genes (e.g., MCP-1) only during zinc deficiency, and adequate zinc was required for rosiglitazone to down-regulate pro-inflammatory markers such as iNOS. In addition, rosiglitazone increased IκBα protein expression only in zinc adequate mice. Finally, plasma data from LDL-R-deficient mice suggest an overall pro-inflammatory environment during zinc deficiency and support the concept that zinc is required for proper anti-inflammatory or protective functions of PPAR. Conclusions: These studies suggest that zinc nutrition can markedly modulate mechanisms of the pathology of inflammatory diseases such as atherosclerosis.

Original languageEnglish
Pages (from-to)577-587
Number of pages11
JournalJournal of the American College of Nutrition
Volume27
Issue number5
StatePublished - Oct 1 2008
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Blood Vessels
Zinc
rosiglitazone
Endothelial Cells
Monocytes
Cultured Cells
E-Selectin
LDL Receptors
Transcriptional Activation

Keywords

  • Endothelial cells
  • Inflammation
  • LDL-R-deficient mouse
  • NF-κB
  • PPAR
  • Zinc deficiency

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-κB and PPAR signaling. / Shen, Huiyun; Oesterling, Elizabeth; Stromberg, Arnold; Toborek, Michal; MacDonald, Ruth; Toborek, Michal J.

In: Journal of the American College of Nutrition, Vol. 27, No. 5, 01.10.2008, p. 577-587.

Research output: Contribution to journalArticle

Shen, Huiyun ; Oesterling, Elizabeth ; Stromberg, Arnold ; Toborek, Michal ; MacDonald, Ruth ; Toborek, Michal J. / Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-κB and PPAR signaling. In: Journal of the American College of Nutrition. 2008 ; Vol. 27, No. 5. pp. 577-587.
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