Cholesterol Transport and Cardiovascular Health

Cholesterol transport underpins the development and prevention of cardiovascular disease through a finely tuned network of lipid carriers, enzymes and cellular transporters. Low-density lipoproteins (LDL) deliver cholesterol to peripheral cells, where excess uptake can lead to arterial wall accumulation and atherogenesis. In contrast, high-density lipoproteins (HDL) mediate reverse cholesterol transport, collecting excess cellular cholesterol and exporting it to the liver for excretion. Key transporters such as ATP-binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor BI (SR-BI), together with enzymes including lecithin–cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP), govern lipid flux and particle remodelling. Beyond lipid shuttling, HDL particles exert antioxidant, anti-inflammatory and endothelial-protective effects, often determined by particle size, protein cargo and enzyme association. Impairment of HDL function or alterations in lipoprotein composition are linked to heightened cardiovascular risk. Recent advances have focused on functional assays rather than static cholesterol concentrations to assess risk, while therapeutic strategies aim to enhance cholesterol efflux capacity or restore HDL protective functions. A global burden of cardiovascular disease has driven research into novel biomarkers and interventions, from precision diagnostics to HDL-targeted therapies, with the ultimate goal of reducing morbidity and mortality through improved management of cholesterol transport pathways.

Research from Nature Portfolio

Advances in proteomic sensor technology have enabled the quantification of an atheroprotective subset of HDL enriched with paraoxonase 1 (PON1). A novel nanoparticle-gated electrokinetic membrane sensor (NGEMS) platform rapidly measures PON1-HDL in plasma without enzymatic interference or extensive sample preparation. This platform achieves sub-picomolar sensitivity and a wide dynamic range, and in preliminary studies demonstrates superior cardiovascular risk discrimination compared with conventional lipid profiles. Implementation of such high-throughput diagnostics could facilitate early risk stratification and guide personalised preventive strategies on a population scale.

Cholesterol Transport and Cardiovascular Health publication trend

The graph below shows the total number of articles in cholesterol transport and cardiovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

High-density lipoprotein (HDL): A class of plasma lipoproteins that transports cholesterol from peripheral tissues to the liver and exerts antioxidant and anti-inflammatory effects.

Reverse cholesterol transport (RCT): The multi-step process by which excess cellular cholesterol is effluxed to HDL and delivered to the liver for excretion.

Cholesterol efflux capacity (CEC): A functional measure of HDL’s ability to accept cholesterol from cells, reflecting its protective potential against atherosclerosis.

ATP-binding cassette transporter A1 (ABCA1): A membrane protein that exports cellular cholesterol and phospholipids to form nascent HDL particles.

Paraoxonase 1 (PON1): An enzyme bound to HDL that contributes antioxidant activity and enhances the cardioprotective properties of the lipoprotein.

References

1. Quantifying PON1 on HDL with nanoparticle-gated electrokinetic membrane sensor for accurate cardiovascular risk assessment. Nature Communications (2023).
2. Flipped C-Terminal Ends of APOA1 Promote ABCA1-Dependent Cholesterol Efflux by Small HDLs. Circulation (2023).
3. Deciphering structural aspects of reverse cholesterol transport: mapping the knowns and unknowns. Biological Reviews (2023).