Dataset Information

Redundancy of IL-1 Isoform Signaling and Its Implications for Arterial Remodeling.

ABSTRACT:

Aims

Mice deficient in IL-1 receptor 1 (hence unresponsive to both IL-1 isoforms ? and ?) have impaired expansive arterial remodeling due to diminished expression of matrix-degrading enzymes, especially MMP-3. Emergence of IL-1 as a target in cardiovascular disease prompted the investigation of the redundancy of IL-1? and IL-1? in the induction of MMP-3 and other matrix-remodeling enzymes in human cells.

Methods and results

Human primary vascular smooth muscle cells (VSMCs) and carotid endarterectomy specimens were stimulated with equimolar concentrations of IL-1? or IL-1? and analyzed protease expression by immunoblot and ELISA. Either IL-1? or IL-1? increased the expression of pro-MMP-3 in VSMCs, facilitated VSMC migration through Matrigel, and induced MMP-3 production in specimens from atheromatous plaques. VSMCs also secreted MMP-1 and Cathepsin S (CatS) upon stimulation with IL-1? or IL-1?. IL-1 isoforms similarly increased MMP-1 and MMP-9 expression in carotid endarterectomy specimens. We examined the expression of MMP-3 and IL-1 isoforms by immunostaining of carotid atheromata, calculated the % positive areas, and tested associations by linear regression. MMP-3 colocalized with IL-1 isoforms in atheromata. MMP-3+ area in plaques positively associated with IL-1?+ (R2 = 0.61, P<0.001) and with IL-1? + areas (R2 = 0.68, P<0.001). MMP-3+ area within atheroma also associated with CD68+ area, but not with ?-smooth muscle actin area.

Conclusions

Either IL-1? or IL-1? can induce the expression of enzymes implicated in remodeling of the arterial extracellular matrix, and facilitate human VSMC migration in vitro. Human atheromata contain both IL-1 isoforms in association with immunoreactive MMP-3. This redundancy of IL-1 isoforms suggests that selective blocking of one IL-1 isoform should not impair expansive arterial remodeling, a finding with important clinical implications for therapeutic targeting of IL-1 in atherosclerosis.

SUBMITTER: Beltrami-Moreira M

PROVIDER: S-EPMC4816548 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Redundancy of IL-1 Isoform Signaling and Its Implications for Arterial Remodeling.

Beltrami-Moreira Marina M Vromman Amélie A Sukhova Galina K GK Folco Eduardo J EJ Libby Peter P

PloS one 20160331 3

<h4>Aims</h4>Mice deficient in IL-1 receptor 1 (hence unresponsive to both IL-1 isoforms α and β) have impaired expansive arterial remodeling due to diminished expression of matrix-degrading enzymes, especially MMP-3. Emergence of IL-1 as a target in cardiovascular disease prompted the investigation of the redundancy of IL-1α and IL-1β in the induction of MMP-3 and other matrix-remodeling enzymes in human cells.<h4>Methods and results</h4>Human primary vascular smooth muscle cells (VSMCs) and ca ...[more]

PMID: 27032103

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Dataset Information

Redundancy of IL-1 Isoform Signaling and Its Implications for Arterial Remodeling.

Aims

Methods and results

Conclusions

Publications

Redundancy of IL-1 Isoform Signaling and Its Implications for Arterial Remodeling.

Similar Datasets

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