Quantifying PON1 on HDL with nanoparticle-gated electrokinetic membrane sensor for accurate cardiovascular risk assessment

Sonu Kumar, Nalin Maniya, Ceming Wang, Satyajyoti Senapati () and Hsueh-Chia Chang ()
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Sonu Kumar: University of Notre Dame
Nalin Maniya: University of Notre Dame
Ceming Wang: University of Notre Dame
Satyajyoti Senapati: University of Notre Dame
Hsueh-Chia Chang: University of Notre Dame

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Cardiovascular disease-related deaths (one-third of global deaths) can be reduced with a simple screening test for better biomarkers than the current lipid and lipoprotein profiles. We propose using a highly atheroprotective subset of HDL with colocalized PON1 (PON1-HDL) for superior cardiovascular risk assessment. However, direct quantification of HDL proteomic subclasses are complicated by the peroxides/antioxidants associated with HDL interfering with redox reactions in enzymatic calorimetric and electrochemical immunoassays. Hence, we developed an enzyme-free Nanoparticle-Gated Electrokinetic Membrane Sensor (NGEMS) platform for quantification of PON1-HDL in plasma within 60 min, with a sub-picomolar limit of detection, 3–4 log dynamic range and without needing sample pretreatment or individual-sample calibration. Using NGEMS, we report our study on human plasma PON1-HDL as a cardiovascular risk marker with AUC~0.99 significantly outperforming others (AUC~0.6–0.8), including cholesterol/triglycerides tests. Validation for a larger cohort can establish PON1-HDL as a biomarker that can potentially reshape cardiovascular landscape.

Date: 2023
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DOI: 10.1038/s41467-023-36258-w

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