TY - JOUR
T1 - Upregulation of Protein Kinase Cδ in Vascular Smooth Muscle Cells Promotes Inflammation in Abdominal Aortic Aneurysm
AU - Schubl, Sebastian
AU - Tsai, Shirling
AU - Ryer, Evan J.
AU - Wang, Chunjie
AU - Hu, June
AU - Kent, K. Craig
AU - Liu, Bo
N1 - Funding Information:
This work was supported by a Public Health Service Grant R01 HL-081424 (K. Kent and B. Liu) from National Heart, Lung, and Blood Institute, an American Heart Association Grant-in-Aid 0455859T (B. Liu), National Institutes of Health training grants T32 GM008466 (E. Ryer and S. Tsai), and T32 HL083824 (S. Schubl), and Society of University Surgeons Scholarship Grant (S. Tsai). The authors thank Sophia Chu for the preparation of adenoviruses, and Drs. Fan Zhang and Domenick Falcone for technical assistance and advice.
PY - 2009/5/15
Y1 - 2009/5/15
N2 - 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.
AB - 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.
KW - abdominal aortic aneurysms
KW - aneurysm formation
KW - monocyte chemotactic factor-1
KW - protein kinase Cδ
KW - vascular inflammation
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U2 - 10.1016/j.jss.2008.04.032
DO - 10.1016/j.jss.2008.04.032
M3 - Article
C2 - 18952226
AN - SCOPUS:67349250115
SN - 0022-4804
VL - 153
SP - 181
EP - 187
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -