Paraoxonase Activity and Cardiovascular Disease Risk
Summary
Paraoxonase enzymes, notably paraoxonase 1 (PON1), play a central role in modulating oxidative stress and inflammation within the vasculature. Predominantly associated with high-density lipoprotein (HDL), PON1 hydrolyses lipid peroxides and homocysteine thiolactone, thereby protecting low-density lipoprotein (LDL) from oxidative modification and attenuating atherogenesis. Genetic polymorphisms of PON1 influence enzyme concentration and catalytic efficiency, creating inter-individual variability in cardiovascular risk. Beyond PON1, paralogues PON2 and PON3 contribute to intracellular antioxidant defences and HDL-bound anti-atherogenic activities, respectively. Environmental factors such as diet, pharmacological agents and comorbidities further modulate PON activity. Cumulative evidence supports a model in which optimal paraoxonase function preserves endothelial homeostasis, inhibits foam cell formation and reduces plaque vulnerability. Advances in assays to measure PON1 activity and in understanding its regulatory mechanisms hold promise for novel diagnostic and therapeutic strategies to mitigate cardiovascular disease at a global scale.
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Paraoxonase Activity and Cardiovascular Disease Risk publication trend
The graph below shows the total number of articles in paraoxonase activity and cardiovascular disease risk across all publications each year (not limited to Nature Index journals).
Technical terms
Paraoxonase 1 (PON1): A calcium-dependent enzyme bound to HDL that hydrolyses oxidised lipids and detoxifies homocysteine thiolactone, thereby protecting against atherosclerosis.
High-density lipoprotein (HDL): A class of lipoprotein that transports excess cholesterol from peripheral tissues to the liver for excretion.
Oxidative stress: An imbalance between reactive oxygen species production and antioxidant defences, leading to cellular damage.
Polymorphism: A genetic variation at a single nucleotide position that may affect gene function or expression.
Palmitoyl-protein thioesterase: An enzymatic activity that removes palmitoyl fatty acids from membrane proteins, regulating their localisation and function.
References
- The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1. Antioxidants (2024).
- PON1 has palmitoyl‐protein thioesterase (PPT) activity, and can affect the presence of SR‐B1 on the endothelial cell membrane. BioFactors (2023).
- Joint effects of paraoxonase 1 rs662 polymorphism and vitamins C/E intake on coronary artery disease severity (Gensini and SYNTAX scores) and lipid profile in patients undergoing coronary angiography. Frontiers in Nutrition (2023).
- Calcium-dependent Human Serum Homocysteine Thiolactone Hydrolase A PROTECTIVE MECHANISM AGAINST PROTEINN-HOMOCYSTEINYLATION*. Journal of Biological Chemistry (2000).
- The Catalytic Histidine Dyad of High Density Lipoprotein-associated Serum Paraoxonase-1 (PON1) Is Essential for PON1-mediated Inhibition of Low Density Lipoprotein Oxidation and Stimulation of Macrophage Cholesterol Efflux*. Journal of Biological Chemistry (2006).
- Paraoxonase-2 Is a Ubiquitously Expressed Protein with Antioxidant Properties and Is Capable of Preventing Cell-mediated Oxidative Modification of Low Density Lipoprotein*. Journal of Biological Chemistry (2001).
- Serum paraoxonase 1 (PON1) measurement: an update. BMC Veterinary Research (2014).
- The paraoxonase 1, 2 and 3 in humans. Biochemia Medica (2011).
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