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

20 Citations (Scopus)

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

Fingerprint

Vascular Diseases
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Death
Cell Proliferation
Apoptosis
Carotid Arteries
Down-Regulation
Platelet-Derived Growth Factor
Transcription Factor AP-1
Adenoviridae
Small Interfering RNA

Keywords

  • Activator protein 1
  • Programmed cell death 4

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

An essential role of PDCD4 in vascular smooth muscle cell apoptosis and proliferation : Implications for vascular disease. / Liu, Xiaojun; Cheng, Yunhui; Yang, Jian; Krall, Thomas J.; Huo, Yuqing; Zhang, Chunxiang.

In: American Journal of Physiology - Cell Physiology, Vol. 298, No. 6, 01.06.2010, p. C1481-C1488.

Research output: Contribution to journalArticle

Liu, Xiaojun ; Cheng, Yunhui ; Yang, Jian ; Krall, Thomas J. ; Huo, Yuqing ; Zhang, Chunxiang. / An essential role of PDCD4 in vascular smooth muscle cell apoptosis and proliferation : Implications for vascular disease. In: American Journal of Physiology - Cell Physiology. 2010 ; Vol. 298, No. 6. pp. C1481-C1488.
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