Session Title: Vasculitis
Session Type: Abstract Submissions (ACR)
The pathophysiology of GCA is poorly understood. Questions remain regarding the mechanisms underlying vascular remodeling.
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.
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
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.
K. H. Ly,
C. Le Jeunne,
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-migration-and-proliferation-potential-characterize-vascular-smooth-muscle-cells-from-patients-with-giant-cell-arteritis/