Tissue and Serum Angiogenic Activity Is Associated With Low Prevalence of Ischemic Complications in Patients With Giant-Cell Arteritis

Abstract

Background— Vascular inflammatory lesions from patients with giant-cell arteritis show a remarkable amount of neovascularization, but its clinical implications have never been investigated. Methods and Results— To assess the clinical relevance of neovascularization in giant-cell arteritis, angiogenesis was measured in temporal artery sections from 31 patients with biopsy-proven giant-cell arteritis by staining endothelial cells with Ulex europaeus lectin. Angiogenesis was highly variable among these patients. Patients without ischemic complications had higher tissue angiogenesis scores than patients with ischemic events (5.69±0.6 versus 2.91±0.6, P =0.003). Angiogenesis was also more prominent in patients with a strong acute phase response (score: 5.31±0.6) compared with those with a weak systemic inflammatory reaction (2.30±0.44; P =0.0007). Serum angiogenic activity was studied in an additional series of 38 biopsy-proven patients. Sera from patients without ischemic events tended to be more active in stimulating human umbilical vein endothelial cell growth (optical density ×1000, 270±15 versus 192±14, P =0.065) and differentiation into capillary-like structures (107±5 versus 84±8 relative units, P =0.0058) than patients with ischemic complications. Sera from patients without ischemic events had more in vivo full angiogenic activity tested in the chick chorioallantoic membrane than sera from patients with ischemic complications. Conclusion— Inflammation-induced angiogenic activity may play a compensatory role for ischemia in patients with giant-cell arteritis.

Risk factors for visual loss in an Italian population‐based cohort of patients with giant cell arteritis

“…The same authors described a weaker angiogenic response in GCA patients with ischemic events and in those with low systemic inflammatory response (21). Finally, they found that IL-6 is able to stimulate endothelial cell proliferation and differentiation into capillary-like structures and to exert a full angiogenic activity in ex vivo (aortic ring) and in vivo 296 Salvarani et al…”

Anti‐interleukin‐6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases

“…This study also found that four PMR patients became disease-free. Several studies, however, have suggested that patients with a lower inflammatory response without an increase in IL-6 expression were at a higher risk of developing ischemic manifestations than were other patients [92], since the angiogenic activity of IL-6 offers protection against ischemia in GCA [93]. These findings indicate that further clinical studies are required to evaluate the efficacy and safety of tocilizumab for GCA and Takayasu arteritis.…”

Elevated Production of Interleukin-6 Is Associated With a Lower Incidence of Disease-Related Ischemic Events in Patients With Giant-Cell Arteritis

“…[13][14][15] Cells were grown until confluence, passed at a ratio of 1 to 4, and used for experiments after the second to fourth passages. Recombinant IL-6 and recombinant soluble IL-6 receptor (sIL-6R) (both from R&D Systems) were diluted in RPMI 1640 (Invitrogen) with 0.1% bovine serum albumin (Sigma) to make a stock solution of 1 and 10 ng/L, respectively.…”

“…Recombinant IL-6 and recombinant soluble IL-6 receptor (sIL-6R) (both from R&D Systems) were diluted in RPMI 1640 (Invitrogen) with 0.1% bovine serum albumin (Sigma) to make a stock solution of 1 and 10 ng/L, respectively. Confluent HUVECs were released with trypsin-EDTA (Invitrogen) and resuspended in complete growth medium 13 diluted at 50% in plain RPMI 1640. Cells were plated in flat-bottomed 96-well plates at 5000 cells/well, with the addition of recombinant IL-6 and/or recombinant sIL-6R at various concentrations, and incubated at 37°C in 5% CO 2 for 1 to 4 days.…”

“…We hypothesized that IL-6 might have direct effects on vessel wall components that might contribute to prevent ischemic events. Given our previous findings that the angiogenic response is lower in those patients with GCA who have ischemic events and in patients with a weak systemic inflammatory response, 13 we subsequently investigated the potential role of IL-6 in triggering endothelial cell responses related to angiogenesis and the ability of IL-6 to induce full angiogenic activity in ex vivo and in vivo models.…”