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

Alexis Regent^1,2, 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: cell biology, cell modulation, giant cell arteritis and vasculitis

Session Information

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 betweenTAB^–-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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