The role of EMMPRIN/CD147 in regulating angiogenesis in patients with psoriatic arthritis
- PDF / 1,266,431 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 53 Downloads / 182 Views
RESEARCH ARTICLE
Open Access
The role of EMMPRIN/CD147 in regulating angiogenesis in patients with psoriatic arthritis Michal A. Rahat1,2*, Mirna Safieh1,3, Elina Simanovich1, Eliran Pasand1,3, Tal Gazitt3, Amir Haddad3, Muna Elias3 and Devy Zisman2,3*
Abstract Background: Angiogenesis plays a central role in the pathophysiology of rheumatic diseases. Patients with psoriatic arthritis (PsA) demonstrate increased vascularity over patients with rheumatoid arthritis (RA), with unknown mechanisms. Methods: We evaluated the serum levels of several pro- and anti-angiogenic factors in 62 PsA patients with active disease, 39 PsA patients in remission, 33 active RA patients, and 33 healthy controls (HC). Additionally, we used an in vitro co-culture system of fibroblast (HT1080) and monocytic-like (MM6) cell lines, to evaluate how their interactions affect the secretion of angiogenic factors and angiogenesis promoting abilities using scratch and tube formation assays. Results: PsA patients, regardless of disease activity, exhibited higher levels of EMMPRIN/CD147, IL-17, and TNF-α relative to RA patients or HC. Factors, such as IL-6, and the ratio between CD147 and thrombospondin-1, exhibited elevated levels in active PsA patients relative to PsA patients in remission. Secretion of CD147, VEGF, and MMP-9 was increased in vitro. CD147 neutralization with an antibody reduced these levels and the ability of endothelial cells to form tube-like structures or participate in wound healing. Conclusions: CD147 plays a role in mediating angiogenesis in PsA, and the therapeutic possibilities of neutralizing it merit further investigation. Keywords: Psoriatic arthritis (PsA), Angiogenesis, EMMPRIN/CD147, Thrombospondin-1 (Tsp-1)
Background Angiogenesis, the process of sprouting of the new blood vessels from existing ones, is a complex process that requires balance between many pro- and anti-angiogenic factors. Although angiogenesis is mostly studied in the tumoral context, it is also demonstrated in rheumatic diseases to different degrees and has been implicated in * Correspondence: [email protected]; [email protected]; [email protected]; [email protected] 1 Immunotherapy Laboratory, Carmel Medical Center, 3436212 Haifa, Israel 2 Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 3109601 Haifa, Israel Full list of author information is available at the end of the article
their pathophysiology [1]. The increased immune infiltrate demands more oxygen than is locally available, resulting in hypoxia [2], which is a potent inducer of angiogenesis. Thus, angiogenesis supports the inflammatory process, and these two processes are inseparable. Interestingly, patients with psoriatic arthritis (PsA) tend to show increased vascularity and higher levels of synovial pro-angiogenic factors than patients with rheumatoid arthritis (RA) [3], and their blood vessels are more tortuous in comparison to RA patients that show straight and branching vasculature [4, 5]. However, the
© The Author(s). 202
Data Loading...
