TY  - JOUR
T1  - Longitudinal Changes in Hemostatic Protein Cargo of LDL-Precipitated Extracellular Vesicles Are Superior to Conventional Biomarkers in Predicting Favorable Left Ventricular Remodeling Post-Myocardial Infarction
A1  - Carlos R. Mendoza
A1  - Li Wei
A1  - Ahmad K. El Sherif
JF  - Bulletin of Pioneering Researches of Medical and Clinical Science
JO  - Bull Pioneer Res Med Clin Sci
SN  - 3006-2659
Y1  - 2023
VL  - 3
IS  - 2
DO  - 10.51847/aYk8eR7pP6
SP  - 121
EP  - 133
N2  - A distinct group of plasma extracellular vesicles (EVs) that co-isolate with low-density lipoprotein (LDL-EVs) contains proteins involved in coagulation and fibrinolytic pathways. This work examined whether the balance between these hemostatic and fibrinolysis-related proteins within LDL-EVs corresponds to patterns of post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling, a process that can lead to heart failure. Levels of von Willebrand factor (VWF), SerpinC1, and plasminogen were quantified in LDL-EVs obtained from plasma at baseline (≤72 h after AMI), 1 month, and 6 months in a cohort of 198 individuals. Based on the 6-month change in LV end-systolic volume (≥15 increase vs. ≥15 decrease), participants were assigned to adverse (n = 98) or reverse (n = 100) remodeling categories. A multilevel longitudinal structural equation modeling (ML-SEM) framework was applied to determine predictive value independent of baseline status. At the baseline sampling point, LDL-EV cargo levels of VWF, SerpinC1, and plasminogen were comparable between the two remodeling groups. By 1 month in the adverse-remodeling group, VWF and SerpinC1 showed declines, while plasminogen rose. Conversely, in those showing reverse remodeling, VWF and plasminogen fell, with SerpinC1 showing no major change. Ultimately, compared with the adverse group, individuals with reverse remodeling displayed higher SerpinC1 and VWF but reduced plasminogen, yielding elevated VWF: Plasminogen and SerpinC1:Plasminogen ratios at both 1 and 6 months. Importantly, the ratios VWF: Plasminogen (AUC = 0.674) and SerpinC1: Plasminogen (AUC = 0.712) offered substantially better prognostic discrimination than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467), or troponin-T (AUC = 0.389) (p < 0.001). Shifts over time in LDL-EV-associated coagulation/fibrinolysis ratios outperform established circulating biomarkers for forecasting post-AMI reverse remodeling. These results may help point to cellular mechanisms involved in structural recovery of the LV following AMI.
UR  - https://bprmcs.com/article/longitudinal-changes-in-hemostatic-protein-cargo-of-ldl-precipitated-extracellular-vesicles-are-supe-1qsbm43zi50878u
ER  -