An essential role of PDCD4 in vascular smooth muscle cell apoptosis and proliferation: Implications for vascular disease

Xiaojun Liu, Yunhui Cheng, Jian Yang, Thomas J. Krall, Yuqing Huo, Chunxiang Zhang

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

It is well established that vascular smooth muscle cell (VSMC) apoptosis and proliferation are critical cellular events in a variety of human vascular diseases. However, the molecular mechanisms involved in controlling VSMC apoptosis and proliferation are still unclear. In the current study, we have found that programmed cell death 4 (PDCD4) is significantly downregulated in balloon-injured rat carotid arteries in vivo and in platelet-derived growth factor-stimulated VSMCs in vitro. Overexpression of PDCD4 via adenovirus (Ad-PDCD4) increases VSMC apoptosis in an apoptotic model induced by serum deprivation. In contrast, VSMC apoptosis is significantly decreased by knockdown of PDCD4 via its small interfering RNA. In the rat carotid arteries in vivo, VSMC apoptosis is increased by Ad-PDCD4. We have further identified that activator protein 1 is a downstream signaling molecule of PDCD4 that is associated with PDCD4-mediated effects on VSMC apoptosis. In addition, VSMC proliferation was inhibited by overexpression of PDCD4. The current study has identified, for the first time, that PDCD4 is an essential regulator of VSMC apoptosis and proliferation. The downregulation of PDCD4 expression in diseased vascular walls may be responsible for the imbalance of VSMC proliferation and apoptosis. The results indicate that PDCD4 may be a new therapeutic target in proliferative vascular diseases.

Original languageEnglish (US)
Pages (from-to)C1481-C1488
JournalAmerican Journal of Physiology - Cell Physiology
Volume298
Issue number6
DOIs
StatePublished - Jun 1 2010

Keywords

  • Activator protein 1
  • Programmed cell death 4

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'An essential role of PDCD4 in vascular smooth muscle cell apoptosis and proliferation: Implications for vascular disease'. Together they form a unique fingerprint.

  • Cite this