Abstract 1162: Proteomic Characterization of the Secretome of Peripheral Blood-derived Smooth Muscle Progenitors
Background. Recent studies on circulating progenitor cells of the myeloid lineage have led to a new appreciation of their secretome, as paracrine factors may support tissue regeneration.
Methods and Results. Using a mass-spectrometry-based proteomic approach complemented by protein separation using two-dimensional gel electrophoresis, we compared the conditioned medium of plasma-derived smooth muscle progenitors (SPCs) and human aortic smooth muscle cells (SMCs). In total, over 150 individual protein features were identified. The majority of proteins were common to both cell lines, but higher amounts of the interstitial collagenase MMP-1, and of inflammatory cytokines, i.e. IL-8 and MCP-1, were found in the conditioned medium of SMCs compared to SPCs, which was subsequently verified by multiplex cytokine assays. ELISA measurements also confirmed that the concentrations of MMP-1 in the conditioned medium of SMCs exceeded the levels in the supernatant of SPCs. Although MMP-1 activity was partially antagonized in SMCs by a coordinated increase in TIMP-1, MMP-1 activity remained lower in SPCs. As a functional consequence, SMCs shedded more N-cadherin, an established MMP target, from their cell surface and showed a stronger invasive capacity. In contrast, SPCs produced more collagen, fibronectin and biglycan, but less perlecan than SMCs. A proteomic comparison between SPCs and endothelial progenitor cells (EPCs) revealed that the production of extracellular matrix proteins and the attenuated secretion of inflammatory cytokines was a specific characteristic of SPCs. EPCs secreted high levels of cathepsins, predominantly cathepsin D, B, Z and L, which were not detected in the conditioned medium of SPCs.
Conclusion. The present study constitutes the first comprehensive assessment of different circulating progenitors of the myeloid lineage demonstrating that apart from their potential physical contribution to lesion formation, SPCs might contribute to plaque stability by limiting inflammatory reactions and contributing to extracellular matrix deposition.