Differential effects of insulin-like growth factor-1 and atheroma-associated cytokines on cell proliferation and apoptosis in plaque smooth muscle cells of symptomatic and asymptomatic patients with carotid stenosis

Guanghong Jia, Gang Cheng, Devendra K. Agrawal

Research output: Contribution to journalArticle

28 Scopus citations


Morbidity and mortality from atherosclerosis are associated with complicated atherosclerotic lesions due to plaque rupture, which is regulated by a balance between proliferation and apoptosis of vascular smooth muscle cells (VSMC). We examined insulin-like growth factor-1 (IGF-1)-induced survival of plaque VSMC from carotid endarterectomy specimens and investigated the underlying cellular mechanisms in the presence and absence of IL-12 and IFN-γ. Both IL-12 and IFN-γ were strongly expressed in symptomatic atherosclerotic plaques as compared with asymptomatic plaques. In asymptomatic plaque VSMC, IGF-1 induced the survival and proliferation of VSMC and accelerated VSMC into S-phase. IL-12 or IFN-γ inhibited proliferation and VSMC were arrested in the G 0-G 1 phase. IGF-1 markedly inhibited the expression of p27 kip and p21 cip and significantly induced cyclin E and cyclin D. Both cytokines by themselves increased the expression of p27 kip and p21 cip and inhibited cyclin E and cyclin D. On the contrary, in symptomatic VSMC there was already increased apoptosis of VSMC and there was no significant effect of IGF-1 or inflammatory cytokines on proliferation, apoptosis or the expression of p27 kip and p21 cip and cyclin D and E. These data suggest that IGF-1 is more potent in inducing the survival of VSMC from the endarterectomy specimens of asymptomatic patients as compared to that of symptomatic subjects and cytokines associated with atheroma lesions decrease the activity of IGF-1-induced survival in the VSMC of asymptomatic plaques. The different expression and activity of cell cycle regulatory proteins could be responsible for apoptosis of VSMC and destabilization of atherosclerotic plaques.

Original languageEnglish
Pages (from-to)422-429
Number of pages8
JournalImmunology and Cell Biology
Issue number5
Publication statusPublished - Oct 2006


All Science Journal Classification (ASJC) codes

  • Immunology
  • Clinical Biochemistry
  • Cell Biology

Cite this