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