# Serum Amyloid A (SAA) and Its Interaction with High-Density Lipoprotein Cholesterol (HDL-C): A Comprehensive Review

## TL;DR

This paper reviews how the protein SAA interacts with HDL cholesterol, changing its function and contributing to heart disease and other conditions.

## Contribution

The paper provides a comprehensive review of SAA's role in altering HDL function and its implications for cardiovascular disease.

## Key findings

- SAA incorporation into HDL impairs cholesterol efflux and promotes inflammation.
- Elevated SAA levels are linked to coronary artery disease, diabetes, and kidney disease.
- Isoform-specific SAA variations influence HDL interactions and disease outcomes.

## Abstract

Serum Amyloid A (SAA) is an acute-phase apolipoprotein that acts as both a sensitive biomarker of systemic inflammation and an active modulator of lipid metabolism and vascular homeostasis. This review summarises current insights into the interaction between SAA and high-density lipoproteins (HDL), with particular emphasis on its role in inflammation-driven cardiovascular disease (CVD). The incorporation of SAA into HDL markedly alters its composition and function. The displacement of apolipoprotein A-I impairs cholesterol efflux capacity, reduces antioxidative activity, and promotes a pro-inflammatory phenotype, transforming protective HDL into a dysfunctional particle. These changes contribute to endothelial dysfunction, foam cell formation, and atherogenesis. Elevated SAA levels are also associated with adverse cardiovascular and metabolic outcomes, including coronary artery disease, type 2 diabetes, and chronic kidney disease. Isoform-specific variations in SAA–HDL interactions are emerging as key modulators of these effects. This review also discusses emerging therapeutic and nutritional strategies to modulate the SAA–HDL axis, including anti-inflammatory therapies, HDL mimetics, and diet-based interventions. Future research should prioritise the standardisation of SAA measurement, characterisation of isoform-specific functions, and translational studies integrating SAA into cardiovascular risk stratification and therapy.