Blood Proteomic Profiling in Inherited (ATTRm) and Acquired (ATTRwt) Forms of Transthyretin-Associated Cardiac Amyloidosis

• DOI: 10.1021/acs.jproteome.6b00998
• Publication Date: 2017-02-15T03:09:03Z
• Authors: Gloria G. Chan; Clarissa M. Koch; Lawreen H. Connors
• Keywords: Proteome; Cardiac Amyloidosis; Retinol binding protein

Transthyretin-associated forms of cardiac amyloidosis are fatal protein misfolding diseases that can be inherited (ATTRm) or acquired (ATTRwt). An accurate diagnosis ATTR challenging as biopsy evidence, usually from the affected organ, is required. Precise biomarkers for disease identification and monitoring undiscovered, disease-specific therapeutic options needed, current understanding molecular pathogenesis limited. The aim this study was to investigate compare serum proteomes in ATTRm ATTRwt identify differentially expressed blood proteins were disease-specific. Using multiple-reaction mass spectrometry (MRM-MS), concentrations 160 analyzed samples patients, a healthy control group. Patient sera matched age (≥60 years), gender (male), race (Caucasian). circulating 123/160 significantly different patient vs sera; TTR retinol-binding (RBP4) levels decreased (p < 0.03) compared controls. In ATTRm, 14/123 identified unique group found generally lower than controls; moreover, RBP4 6 other 0.04) ATTRwt. Predicted interactions among 14 categorized reaction binding associations. Alternatively, 27 with associated defined activation, catalysis, inhibition, addition binding. This demonstrates significant proteomic differences between sera, disease-associated variations several including RBP4. may have diagnostic prognostic utility, provide important clues about mechanisms.