LAUSR

Prediction of left ventricular (LV) remodeling post-acute myocardial infarction (AMI) remains challenging. Several circulating biomarkers have been associated with post-AMI LV remodeling, however, there is no biomarker available to distinguish adverse versus reverse LV remodeling. In this study, we aimed to assess the association of extracellular vesicles (EVs) associated proteins with LV remodeling post-AMI. Plasma EVs were isolated via precipitation with dextran sulphate as we previously reported. The protein levels of EV associated von Willebrand factor (VWF), SerpinC1 (antithrombin-III), plasminogen and SerpinF2 (alpha 2-antiplasmin) were determined in the citrate-anticoagulated plasma from 57 healthy subjects and 200 patients recruited in the Post-AMI Left Ventricular Remodeling Biomarker Analysis (PAMILA) study. Patients were categorized into two groups: adverse LV remodeling (n=100) characterized by an increase or reverse LV remodeling (n=100) characterized by a decrease, in LV end systolic volume by ≥15% over 6 months. Patients' plasma was collected at baseline (within 3 days after percutaneous coronary intervention), 1 month and 6 months post-AMI. Log transformation of EV protein levels was performed for assessment in a multiple multi-level longitudinal data analysis with structural equation model (with level of significance fixed at 0.05). Compared to healthy subjects, baseline protein levels of EV associated VWF and SerpinF2 were significantly higher in post-AMI patients, whereas no difference was observed in SerpinC1 and plasminogen. Among the patients, those on statins (196 out of 200 patients) showed lower protein levels of EV associated VWF (p<0.001) and plasminogen (p=0.003), whereas patients treated with P2Y12 platelet inhibitors (195 out of 200 patients) showed higher protein levels of EV associated VWF (p=0.003) and plasminogen (p=0.035). Multiple multi-level longitudinal data analysis with structural equation model showed that protein levels of EV associated VWF (p<0.001) and SerpinC1 (p=0.021) were lower in patients with adverse LV remodeling than that in patients with reverse LV remodeling during the 6-month follow-up post-AMI. In contrast, protein levels of EV associated plasminogen (p=0.002) and SerpinF2 (p=0.002) were higher in patients with adverse LV remodeling. The differences in the four EV associated proteins between patients with adverse versus reverse LV remodeling remain significant after adjusting for age, gender, ethnicity, medications, lipid profile and risk factors (diabetes, hypertension, dyslipidemia and smoking). Lower levels of EV associated coagulation proteins (VWF and SerpinC1) and higher levels of EV associated fibrinolytic proteins (plasminogen and SerpinF2) were presented in patients with adverse LV remodeling compared to those with reverse LV remodeling post-AMI. National University Health System Singapore (NUHS O-CRG 2016 Oct-23) to JW Wang