Abstract 15451: The Novel Mechanistic and Diagnostic Role of Tie-2+cd14+ Monocytes in Patients with a Thoracic Aortic Aneurysm
Thoracic aortic aneurysm (TAA) is a dangerous disease with high mortality, and is associated with extracellular matrix (ECM) remodeling and increased matrix metalloprotease activity (MMP) in the aortic wall. Tie-2 expressing monocytes (TEMs) produce MMPs and are involved in ECM remodeling in malignancies; but their role in TAA is unknown. Ninety-eight TAA patients and 10 control heart donors were included in this study. Circulating TEM count was measured by flow cytometry and serum angiopoietin-2 (Ang-2) by ELISA. Immunohistochemistry analyzed TEMs, Ang-2 and MMP-9 in aortic tissue. The mean circulating TEM fraction of peripheral blood mononuclear cells (PBMC) in the pooled TAA patient cohort was higher (5.76% ± 9.2; p<0.001) than controls (0.57% ± 0.4). Patients with progressive TAA had a higher TEM fraction (5.11% ± 3.8) versus those with constant TAA (3.14% ± 5.0, p=0.04). TEMs, however, were not associated with the size of the aneurysm (rs=0.13; p=0.62), patient age (rs=0.23; p=0.53) or gender (rs=0.11; p=0.31). TEMs were localized in the aortic tunica adventitia and media in close vicinity of vasa vasorum; and their number was higher in TAA patients compared to controls (p=0.02). In ROC curve analysis, circulating TEMs at a cut off level of 1% identified TAA with a sensitivity of 80% and a specificity of 78% (AUC: 0.91, p< 0.0001). TEMs at a cut off level of 1.8% identified patients with progressive TAA with a sensitivity of 75% and a specificity of 78% (AUC: 0.80, p=0.047). TAA patients had significantly higher circulating Ang-2 concentrations (2985.49 pg/ml ± 1631.1) compared to controls (1489.52 pg/ml ± 402.3; p<0.001). However, Ang-2 serum concentrations did not correlate with age (rs=0.11; p=0.07), gender (rs=0.1; p=0.21), maximal aortic diameter (rs=0.20; p=0.24), aneurysm progression (rs=0.03; p=0.52). Ang-2, a chemoattractant for TEMs, and MMP-9 were more abundantly present in the aortic tunica adventitia of TAA patients compared to controls (p<0.01). This study identified TEMs as novel players in the clinical development of TAA associated with tissue remodeling. TEMs might serve as a surrogate quantitative marker for TAA and monitoring its progression.
- © 2012 by American Heart Association, Inc.