Abstract 20249: Microparticles From Systemic Sclerosis Patients May Affect Vascular Inflammation of Endothelial Cells In Vitro
Introduction: Microparticles (MPs) are submicron vesicles released from cells both in health and in response to inflammation, apoptosis, or shear stress. Prior investigations have suggested that MPs may play an active role in endothelial dysfunction through paracrine signaling, but it is unknown if MPs obtained from patients with systemic sclerosis (SSc) participate in the pathogenesis of vascular dysfunction in SSc.
Hypothesis: Human aortic endothelial cells (HAECs) exposed in vitro to MPs obtained from SSc patients will express more inflammatory mediators compared to exposure of HAECs to MPs from healthy controls.
Methods: MPs were isolated from 10 SSc patients (5 with pulmonary hypertension) and 10 healthy controls through differential centrifugation of peripheral venous blood. HAECs were cultured to 80% confluence and then exposed for 12 or 24 hours to MPs from SSc patients or healthy controls. ICAM-1, VCAM-1, and MCP-1 were quantified in triplicate by RT-PCR and expressed as fold-change compared to HAECs not exposed to MPs.
Results: After 12 hours of exposure, HAECs exposed to MPs from SSc patients exhibited an increase in ICAM-1 (1.53±0.09 vs. 1.29±0.03 fold change, p=0.01) and VCAM-1 (0.92±0.07 vs. 0.76±0.03 fold change, p=0.03) compared to MPs from healthy controls, but no difference in MCP-1 was seen (0.98±0.03 vs. 0.97±0.11 fold change, p=0.94). After 24 hours of exposure, HAECs exposed to MPs from SSc patients had an increase in ICAM-1 (1.05±0.01 vs. 0.93±0.05 fold change, p=0.02) and MCP-1 (1.53±0.03 vs. 1.28±0.06, p=0.003) compared to MPs from controls, but no difference in VCAM-1 was demonstrated (1.40±0.05 vs. 1.33±0.07, p=0.16).
Conclusions: HAECs exposed to microparticles obtained from SSc patients demonstrated increased expression of inflammatory adhesion molecules and MCP-1, a chemokine that regulates monocyte migration. This suggests that MPs in patients with SSc may contribute to propagation of vascular inflammation. Ongoing experiments are investigating the mechanisms of these findings and determining which cell type of origin these MPs are derived from.
Author Disclosures: M.R. Lammi: None. S. Okpechi: None. D. Wyczechowska: None. L.A. Saketkoo: None. N. Bauer: None. K. Pyakurel: None. A. Tarhuni: None. B. deBoisblanc: None. A.H. Boulares: None.
- © 2016 by American Heart Association, Inc.