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

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Proteomics

Background:

• Cardiovascular diseases cause one-third of global deaths, necessitating improved risk assessment beyond current lipid profiles.
• High-density lipoprotein (HDL) subclasses, particularly those with paraoxonase-1 (PON1-HDL), show promise as superior atheroprotective biomarkers.
• Existing methods for quantifying HDL proteomic subclasses are hindered by interfering peroxides and antioxidants, complicating assays.

Purpose of the Study:

• To develop and validate a novel biosensor for accurate and rapid quantification of PON1-HDL in human plasma.
• To establish PON1-HDL as a superior biomarker for cardiovascular risk assessment compared to traditional markers.

Main Methods:

• Development of an enzyme-free Nanoparticle-Gated Electrokinetic Membrane Sensor (NGEMS) platform.
• Quantification of PON1-HDL in human plasma using NGEMS, achieving a sub-picomolar limit of detection and a 3-4 log dynamic range.
• Comparative analysis of NGEMS-based PON1-HDL detection against standard lipid and lipoprotein profiles.

Main Results:

• The NGEMS platform enabled rapid (within 60 minutes) and sensitive quantification of PON1-HDL without sample pretreatment or calibration.
• PON1-HDL demonstrated a high area under the curve (AUC) of approximately 0.99 for cardiovascular risk assessment.
• NGEMS-based PON1-HDL detection significantly outperformed traditional markers like cholesterol and triglycerides (AUC ~0.6-0.8).

Conclusions:

• The NGEMS platform offers a highly sensitive and efficient method for quantifying PON1-HDL.
• PON1-HDL is a potent biomarker for superior cardiovascular risk assessment.
• Further validation in larger cohorts could establish PON1-HDL as a transformative biomarker in cardiovascular medicine.