Circulating Proteomic Signatures Associated with Cardiac Allograft Vasculopathy in Adult and Pediatric Heart...

Cardiac Allograft Vasculopathy (CAV) is a common complication following orthotopic heart transplant (OHT). Detection by coronary angiography is invasive and insensitive. Prior biomarker investigations examined a narrow proteomic range, and age-group differences in the CAV proteome remain undefined. We aimed to quantify the CAV proteome and compare across age groups in a hypothesis-generating manner.

We sampled 35 pediatric and 28 adult OHT recipients from the University of Colorado heart biobanks. CAV was defined angiographically, when blood was sampled for assay of 5,416 plasma proteins. Pediatric recipients contributed longitudinal data for up to two additional time points. Univariable binary logistic regression and univariable ordinal logistic regression assessed associations between protein abundance and prevalent CAV and CAV severity, respectively. Mixed-effects ordinal logistic regression examined longitudinal associations in the pediatric subcohort.

In the overall cohort, 340 and 323 proteins were nominally associated with prevalent CAV and higher CAV grade, respectively; 503 proteins showed nominal effect modification by age group. No cross-sectional associations survived FDR correction. In exploratory pathway analyses, we observed patterns of these nominal protein associations characterized by extracellular matrix remodeling and immune signaling in the overall cohort, innate immunity and vascular inflammation in the pediatric subcohort, and lipid metabolism and vascular biology in the adult subcohort.

In this hypothesis-generating study, circulating proteomic associations with CAV differed between pediatric and adult OHT recipients. These exploratory differences were characterized by immune and vascular inflammatory pathways in children and metabolic and vascular pathways in adults; results require external validation.