BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro- and macrovascular CAV and major adverse cardiac events in HTx patients.

METHODS: We evaluated 91 cardiovascular disease-related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro- and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15 O-H2 O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death.

RESULTS: We found consistent differences in two proteins involved in cholesterol homeostasis; significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p<0.05) and significantly decreased paraoxonase 3 (PON3) (p<0.05). N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly increased in patients with microvascular CAV (p<0.05) and borderline significantly increased in patients experiencing major adverse cardiac events (p=0.10) and patients with macrovascular CAV (p=0.05).

CONCLUSIONS: We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT-proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.