Upregulation of Protein Kinase Cδ in Vascular Smooth Muscle Cells Promotes Inflammation in Abdominal Aortic Aneurysm

Sebastian Schubl, Shirling Tsai, Evan J. Ryer, Chunjie Wang, June Hu, K. Craig Kent, Bo Liu

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: The development of abdominal aortic aneurysms (AAAs) involves a complex interplay of extracellular matrix degradation, inflammation, and apoptosis. We have previously shown that protein kinase Cδ (PKCδ) plays a critical role in vascular smooth muscle cell (vSMC) apoptosis in the setting of oxidative stresses. Here, we show that PKCδ is also involved in the signaling that draws inflammatory cells to aneurismal tissue. Materials and methods: Immunostaining for monocyte chemotactic factor (MCP)-1 and PKCδ was performed on paraffin-fixed arterial sections. Enzyme-linked immunosorbent assay to detect MCP-1 produced by vSMCs was performed on media from cultured rat A10 cells after cytokine induction with or without the PKCδ-specific inhibitor rottlerin. Migration of isolated lymphocytes was evaluated in response to media from activated A10 cells. Results: Human AAAs show widespread and elevated expression of PKCδ that is not seen in normal aortic tissues. Cytokine stimulation of cultured vSMCs induced vigorous production of the key chemotactant MCP-1, the expression of which was PKCδ dependent. Stimulated vSMCs were capable of inducing the migration of leukocytes, and this effect was also dependent on PKCδ activity. Staining of human AAA tissue for MCP-1 showed an expression pattern that was identical to that of PKCδ and smooth muscle specific alpha-actin. Conclusions: PKCδ is widely expressed in human AAA vessel walls and mediates MCP-1 expression by vSMCs, which could contribute to the inflammatory process. These findings, coupled with earlier studies of PKCδ, suggest that PKCδ plays a central role in the pathogenesis of AAAs and may be a potential target for future therapies.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalJournal of Surgical Research
Volume153
Issue number2
DOIs
StatePublished - May 15 2009

Keywords

  • abdominal aortic aneurysms
  • aneurysm formation
  • monocyte chemotactic factor-1
  • protein kinase Cδ
  • vascular inflammation

ASJC Scopus subject areas

  • Surgery

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