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PMID:16942485

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Citation

Jia, G, Cheng, G and Agrawal, DK (2006) 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. Immunol. Cell Biol. 84:422-9

Abstract

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-gamma. Both IL-12 and IFN-gamma 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-gamma inhibited proliferation and VSMC were arrested in the G0-G1 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.

Links

PubMed Online version:10.1111/j.1440-1711.2006.01449.x

Keywords

Aged; Apoptosis; Atherosclerosis/immunology; Carotid Stenosis/immunology; Carotid Stenosis/pathology; Carotid Stenosis/physiopathology; Cell Cycle Proteins/genetics; Cell Proliferation; Cytokines/immunology; Female; Humans; Insulin-Like Growth Factor I/immunology; Male; Middle Aged; Muscle, Smooth, Vascular/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:IFNG

involved_in

GO:0007050: cell cycle arrest

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000359)

Seeded From UniProt

complete

HUMAN:IFNG

involved_in

GO:0097191: extrinsic apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000359)

Seeded From UniProt

complete

HUMAN:IGF1

involved_in

GO:0048661: positive regulation of smooth muscle cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IGF1

involved_in

GO:0034392: negative regulation of smooth muscle cell apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IGF1

involved_in

GO:2001237: negative regulation of extrinsic apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000359)

Seeded From UniProt

complete

HUMAN:IL12A

involved_in

GO:0048662: negative regulation of smooth muscle cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL12A

involved_in

GO:0007050: cell cycle arrest

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000359)

Seeded From UniProt

complete

HUMAN:IL12A

involved_in

GO:0034393: positive regulation of smooth muscle cell apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL12A

involved_in

GO:0097191: extrinsic apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000359)

Seeded From UniProt

complete

HUMAN:IL12B

involved_in

GO:0048662: negative regulation of smooth muscle cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL12B

involved_in

GO:0007050: cell cycle arrest

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000359)

Seeded From UniProt

complete

HUMAN:IL12B

involved_in

GO:0034393: positive regulation of smooth muscle cell apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFNG

involved_in

GO:0034393: positive regulation of smooth muscle cell apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFNG

involved_in

GO:0048662: negative regulation of smooth muscle cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFNG

involved_in

GO:0007050: cell cycle arrest

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0000359)

Seeded From UniProt

complete

HUMAN:IFNG

involved_in

GO:0097191: extrinsic apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0000359)

Seeded From UniProt

complete


See also

References

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