Protein kinase C delta mediates arterial injury responses through regulation of vascular smooth muscle cell apoptosis

Dai Yamanouchi, Kaori Kato, Evan J. Ryer, Fan Zhang, Bo Liu

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Aims A balance between apoptosis and proliferation of vascular smooth muscle cells (VSMC) influences the development of intimal hyperplasia. We have previously demonstrated that protein kinase C delta (PKC) regulates both apoptosis and proliferation of VSMC in vitro. Here we investigate the role of PKC in intimal hyperplasia through gene deletion or overexpression in rodent models of arterial injury.Methods and results Arterial injury was induced in mice and rats by means of carotid ligation or balloon angioplasty, respectively. Overexpression of PKC was achieved by adenovirus-mediated gene transfer immediately after balloon injury in rat carotid arteries. Levels of PKC protein were profoundly increased in the carotid wall 3-7 days after balloon injury, co-localizing to TUNEL-positive medial cells. When subjected to arterial injury, PKC gene-deficient mice responded with an enhanced intimal hyperplasia accompanied by an 80 reduction in the number of TUNEL-positive cells detected in the injured arteries as compared with their wild-type littermates. Conversely, arterial gene transfer of PKC further increased the arterial expression of PKC, which was associated with a marked increase in apoptosis and reduction of intimal hyperplasia. Neither manipulation led to significant alteration in cell proliferation, suggesting that the function of PKC after arterial injury is predominantly pro-apoptotic. This notion is further supported by our observation of high PKC expression in human restenotic lesions that also co-localized with apoptosis.Conclusion The expression of PKC is upregulated in the arterial wall in response to injury. This induction appears to be a mechanism of arterial response that negatively influences the degree of intimal hyperplasia by stimulating VSMC apoptosis.

Original languageEnglish
Pages (from-to)434-443
Number of pages10
JournalCardiovascular Research
Issue number3
Publication statusPublished - 02-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine


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