Session Type: Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and extensive tissue fibrosis of the skin and internal organs. Endothelial cells (ECs), a predominant target of the autoimmune attack, may undergo proliferation arrest, apoptosis, or differentiation to myofibroblasts, leading to complications including pulmonary arterial hypertension (PAH). The differentiation of ECs into myofibroblasts through endothelial mesenchymal transition (EndMT) represents a critical step in the blood vessels remodeling. ECs in the dermal microvascular tissue of patients with SSc exhibit robust expression of CCR3, the cognate receptor of CCL24,which has been found to be elevated in the serum and skin biopsies of SSc patients. The objective of this study is to evaluate the association between serum CCL24 levels and clinical characteristics of SSc patients, as well as the involvement of the CCL24-CCR3 axis in EndMT process.
Methods: CCL24 levels were evaluated in the sera of 75 SSc patients using ELISA. In this cohort, Pearson correlation tests were conducted to determine the relationship between CCL24 levels and performance measures such as the 6-minute walk test (6MW test). To study the potential association of CCL24 and CCR3 with the processes underlying EndMT, we established an in-vitro system in which the combination of TGFβ TNFα induced EndMT in human umbilical vein endothelial cells (HUVECs) and explored the expression of CCR3 and the effect of CCL24 supplementation and anti CCL24 antibody to this system. Studies included functional assessment of proliferation, cell death migration as well as evaluation of multiple markers of EndMT processes including αSMA, Vimentin, SNAIL, CD31 and VE-cadherin.
Results: The average level of CCL24 in the sera of patients with SSc with PAH (n=9) was significantly higher compared to the level of patients with SSc and without PAH (1136 vs 738 pg/ml, p< 0.05). Furthermore, a negative correlation was found between CCL24 levels and the 6MW test performance (r=-0.3, p< 0.05), reflecting reduced exercise capacity. The addition of TGFβ and TNFα resulted in EndMT in HUVECs, which was demonstrated by a significant increase in mesenchymal markers, reduced ECs markers, reduced cell number (52%, p< 0.05), and increased cell migration (112%, p< 0.05) relative to control. Furthermore, the EndMT process was associated with a significant increase in CCR3 levels (197%, p< 0.05). Notably, adding CCL24 in addition to TNFα and TGFβ further reduced cell count (from 52% to 33%, p< 0.05) and increased migration (from 112% to 127%, p=0.07). CCL24 neutralizing antibody (CM-101) completely inhibited cell migration and increased cell number.
Conclusion: This study provides evidence for the potential role of CCL24 in the pathogenesis of SSc and highlights its involvement in EndMT process resulting in disease complications such as PAH.
To cite this abstract in AMA style:Amoyal I, Hornik-Lurie T, Zitman-Gal T, Levy H, Vaknin I, Drucker L, Heusler I, Levy Y, Tartakover Matalon S. The Involvement of CCR3-CCL24 Axis in Endothelial to Mesenchymal Transition Process and Pulmonary Arterial Hypertension in Systemic Sclerosis Patients [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/the-involvement-of-ccr3-ccl24-axis-in-endothelial-to-mesenchymal-transition-process-and-pulmonary-arterial-hypertension-in-systemic-sclerosis-patients/. Accessed .
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-involvement-of-ccr3-ccl24-axis-in-endothelial-to-mesenchymal-transition-process-and-pulmonary-arterial-hypertension-in-systemic-sclerosis-patients/