Dysregulated Proteins in Plasma Distinguishing Syndromic from Non-syndromic Heritable Thoracic Aortic Disease

BACKGROUNDThoracic aortic aneurysms (TAA) are often found in younger individuals and approximately 20% may be associated with heritable thoracic aortic disease (HTAD). There are some data on genomic biomarkers reflecting inflammation and extracellular matrix remodeling in HTAD. However, data that accurately reflect the corresponding protein changes are scarce. Our aim was to quantify proteins by using targeted proteomics in HTAD patients versus healthy controls (HC). METHODSPatients with Loeys-Dietz syndrome (LDS, n = 8), Marfan syndrome (MFS, n = 11), and Aortic aneurysm, familial thoracic 6 syndrome (AAT6, n = 7) were recruited. For comparison, blood samples were drawn from 16 healthy controls (HC). Plasma samples were analyzed by targeted proteome analysis of 276 proteins using immunoaffinity proteomics. RESULTSSeven proteins were elevated when comparing HTAD to HC, displaying two patterns: i) Oncostatin M (OSM) and Pentraxin-3 (PTX3) were significantly higher in both LDS and MFS, with comparable levels in AAT6, reflecting a generalized increase in HTAD. ii) increased levels of TNF Receptor Superfamily Member 9 (TNFRSF9), Granulysin (GNLY), Glycoprotein 1b-alpha (GP1BA), Vasorin (VASN) and CD5 were restricted to the LDS subgroup and correlated positively with Th17 and platelet counts. CONCLUSIONSThe general increase in OSM and PTX3 in HTAD may reflect early but common mechanisms related to vascular inflammation while the distinct increase in TNFRSF9, GNLY, VASN, GP1BA and CD5 in LDS patients, may reflect involvement of Th17 inflammatory response mechanisms in the progression of TAA. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/624213v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1234b26org.highwire.dtl.DTLVardef@1ad982org.highwire.dtl.DTLVardef@bdf438org.highwire.dtl.DTLVardef@ec9c67_HPS_FORMAT_FIGEXP M_FIG C_FIG