ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 783

Increased Migration and Proliferation Potential Characterize Vascular Smooth Muscle Cells from Patients with Giant Cell Arteritis

Alexis Regent1,2, Kim-Heang Ly3, Matthieu Groh2, Chabha Khifer4, Sebastien Lofek4, Guilhem Clary5, Philippe Chafey5, Cédric Broussard5, Christian Federici5, Claire Le Jeunne2, Elisabeth Vidal6, Antoine Brezin7, Veronique witko-Sarsat5, Loïc Guillevin2 and Luc Mouthon2, 1Internal Medicine, Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Paris, France, Paris, France, 2National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, Paris, France, 3Laboratoire d’immunologie, EA3842, Faculté de médecine, Limoges;, Limoges, France, 4Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Paris, France, Paris, France, 5Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Paris, France, 6Laboratoire d’immunologie, EA3842, Faculté de médecine, Limoges, France, 7Service d’ophtalmologie, hôpital Cochin, AP-HP, Paris, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Session Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose

The pathophysiology of GCA is poorly understood. Questions remain regarding the mechanisms underlying vascular remodeling.

Methods

Vascular smooth muscle cells (VSMC) were cultured from temporal artery biopsies (TAB) of consecutive patients suspected of GCA. We selected four patients with biopsy proven GCA (TAB+-GCA), four patients with biopsy-negative GCA (TAB–-GCA), and four patients with another diagnosis than GCA (GCA-control). Normal human aorta VSMC were used as control. Proteomes of VSMC from patients in TAB+-GCA, TAB–-GCA or GCA-control groups were compared using two-dimension DIGE (2D-DIGE) at pH range of 3-11. Transcriptomic analysis of VSMC from patients within the three GCA groups was performed using affimetrix chips. Proliferation of VSMC was performed with BrDU proliferation assay ELISA kit in unstimulated condition and with paxillin siRNA.

Results

We could identify 16, 28 and 2 protein spots that were differentially expressed between VSMC from TAB+-GCA and GCA-control patients, between  TAB+-GCA and TAB–-GCA patients and between TAB–-GCA and GCA-control patients respectively (fold change≥1.5 and p≤0.05). Principal component analysis differentiated VSMC proteomes from TAB+-GCA, TAB–-GCA and GCA-control. Ingenuity analysis comparing TAB+-GCA and aorta revealed that identified proteins interact with paxillin.

Genes differentially expressed between VSMC from patients with TAB+-GCA, TAB–-GCA and GCA-control were involved in cellular movement, organismal injury, tissue development, and cancer.

Unstimulated proliferation and in the presence of paxillin siRNA are currently being investigated in order to evaluate its potential involvement in the dysregulated proliferative phenotype observed in VSMC from GCA patients

Conclusion

VSMC from patients with GCA expressed proteins that confer increased proliferation and migration potential. Inhibition of the increased proliferation of VSMC during GCA through paxillin targeting might represent a promising therapeutic approach in patients with GCA.

Disclosure:

A. Regent,
None;

K. H. Ly,
None;

M. Groh,
None;

C. Khifer,
None;

S. Lofek,
None;

G. Clary,
None;

P. Chafey,
None;

C. Broussard,
None;

C. Federici,
None;

C. Le Jeunne,
None;

E. Vidal,
None;

A. Brezin,
None;

V. witko-Sarsat,
None;

L. Guillevin,
None;

L. Mouthon,
None.

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