Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Methods: We isolated vSMCs from 4mm punch skin biopsies from 3 patients with SSc and 3 healthy controls. We evaluated the expression levels of EDN1, EDNRA and EDNRB, which encodes for ET-1, Endothelin Receptor A (ERA) and ERB, respectively, in vSMCs from SSc patients and controls. We treated vSMCs with ET-1, in the presence or absence of selective ETA antagonist (BQ123), selective ETB antagonist (BQ788) or dual ETA+B antagonist (PD145065). Under these conditions, we examined the effects of ET-1 on cell proliferation using BrdU assay, viability by MTT assay and apoptosis by Tunel assay.
Results: SSc-vSMCs overexpressed EDN1 compared to control vSMCs (120 fold). Furthermore, and compared to control-vSMCs, EDRA expression levels were significantly increased in SSc-vSMCs while EDNRB expression levels were lower than control values. At baseline, SSc-vSMCs exhibited 1.8-fold increase in cell proliferation compared to control vSMCs (P= 0.0031). Upon treating control-vSMCs with 10nM ET-1, we demonstrate increased vSMCs proliferation by 1.6 folds (P= 0.03) in association with decreased cell apoptosis by 36%. The addition of selective ETB antagonist (BQ788) or dual ETA+B antagonist (PD145065) reduced vSMCs proliferation by 72% and 69%, respectively (P<0.05), but we did not find significant effect for selective ETA antagonist (PD156707) on cell proliferation (P>0.05). Moreover, BQ788 and PD145065 increased apoptosis of vSMCs. We did not see this effect using the selective ETA antagonist.
Conclusion: We provide an experimental evidence for increased proliferation, viability and decreased apoptosis of vSMCs by ET-1 in vitro, and we demonstrate that this effect is mediated by ETB receptors. Selective ETB and non-selective ETA+B receptor antagonists have a theoretical advantage over selective ETA antagonists in reducing the effect of ET-1 on proliferation of cells in tunica media, and that ET-1 have an important role in the development of vascular remodeling in SSc.
To cite this abstract in AMA style:Nada S, Wang Y, Altorok N, Kahaleh B. The Role of Endothelin 1 in Activation of Vascular Smooth Muscle Cells in Systemic Sclerosis; Increased Cell Proliferation and Resistance to Apoptosis Mediated By Endotehlin B Receptors [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-role-of-endothelin-1-in-activation-of-vascular-smooth-muscle-cells-in-systemic-sclerosis-increased-cell-proliferation-and-resistance-to-apoptosis-mediated-by-endotehlin-b-receptors/. Accessed September 21, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-endothelin-1-in-activation-of-vascular-smooth-muscle-cells-in-systemic-sclerosis-increased-cell-proliferation-and-resistance-to-apoptosis-mediated-by-endotehlin-b-receptors/