Abstract 15455: Endothelial Cell Specific Molecule-1 (ESM-1), a Novel Secreted Proteoglycan Stimulates Vascular Smooth Muscle Cell Proliferation and Migration
Background: Vascular inflammation plays a critical role in the initiation and progression of atherosclerosis. Endothelial cell specific molecule-1 (ESM-1) or Endocan is a dermatan sulphate proteoglycan expressed and secreted mainly by the vascular endothelium. Elevated levels of ESM-1 are observed in plasma of patients during tumor progression and in inflammatory disorders like sepsis suggesting that it could be potential biomarker for endothelial activation or dysfunction. In this study we investigated the role of ESM-1 during atherosclerotic lesion formation.
Methods and Results: We first studied ESM-1 expression in atherosclerotic plaques of ApoE null mice fed on high fat diet. Immunohistochemistry revealed that ESM-1 is highly expressed in these plaques. In contrast to its low expression in the quiescent endothelium, ESM-1 expression is significantly upregulated in the activated endothelium of the lesions. This suggests that under inflammatory conditions in vivo, ESM-1 expression is augmented in the endothelium. We next studied the effect of pro-inflammatory cytokine TNF-α on ESM-1 protein expression and secretion. In human umbilical vein endothelial cells (HUVECs), TNF-α (10 ng/ml) increased ESM-1 protein expression and secretion in a time dependent manner. Since vascular smooth muscle cell (VSMC) proliferation and migration mediates neointima formation, we hypothesized that secreted ESM-1 increases VSMC proliferation and migration. To test this hypothesis we treated human coronary aortic smooth muscle cells (HCASMCs) with human recombinant ESM-1. We observed a time and dose dependent increase in ERK1/2 phosphorylation peaking at 10 minutes. To gain more insight into the functional significance, we performed a scratch wound assay in HCASMCs to assess cell migration. Wound closure significantly increased by 25% in the presence of human recombinant ESM-1 compared to untreated control cells (*p<0.05). These data suggests that ESM-1 has a positive effect on VSMC proliferation and migration.
Conclusion: Our data provide evidence that ESM-1, a novel endothelial secreted proteoglycan stimulates VSMC proliferation and migration and may contribute to neointima formation during atherosclerosis
- © 2011 by American Heart Association, Inc.