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Updated: Jun 22, 2026

Cholesterol Efflux Assay
Published on: March 6, 2012
Ability of serum to decrease cellular acylCoA:cholesterol acyl transferase activity predicts cardiovascular outcomes
Julio A Chirinos1, Juan P Zambrano, Simon Chakko
1Miller School of Medicine, University of Miami, Miami, FL 33138, USA.
Insights
Serum cholesterol efflux activity, measured by its ability to decrease cholesterol for esterification, independently predicts major adverse cardiovascular events (MACE) and death in men. This finding offers new insights into cardiovascular risk assessment.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Lipid Metabolism
Background:
- Investigated the association between serum cholesterol efflux activity and coronary artery disease (CAD).
- Examined the link between cholesterol efflux and the risk of major adverse cardiovascular events (MACE) and death.
Purpose of the Study:
- To determine if serum cholesterol efflux activity predicts the presence of angiographic CAD.
- To assess the association of cholesterol efflux activity with the risk of MACE and death.
Main Methods:
- Studied 168 men undergoing coronary angiography.
- Measured in vitro cholesterol efflux activity using patient serum and human skin fibroblasts.
- Defined efflux activity by the serum's ability to decrease cholesterol available for acylCoA:cholesterol acyl transferase (ACAT) esterification.
- Followed patients for 4.5 years to track MACE and death.
Main Results:
- Serum-induced changes in ACAT activity did not correlate with HDL levels or CAD presence.
- Patients in the highest tertile of ACAT activity change had significantly higher risk for MACE (HR, 2.15) and death (HR, 2.23).
- These correlations remained independent of other risk markers like LDL, HDL, and C-reactive protein.
Conclusions:
- Serum's ability to deplete cellular cholesterol for ACAT esterification is a strong, independent predictor of MACE and death.
- Speculated that this activity involves ATP binding cassette transporter A1 (ABCA1)-mediated efflux.
- Hypothesized that increased ACAT-influencing HDL particles in serum relate to limited in vivo ABCA1 activity.
Background:
We evaluated whether cholesterol efflux activity of serum is associated with the presence of angiographic coronary artery disease (CAD) and the risk of major adverse cardiovascular events (MACE) and death.
Methods And Results:
We studied 168 men undergoing coronary angiography. Cholesterol efflux activity was measured in vitro by incubation of patient serum with human skin fibroblasts and defined as the ability of serum to decrease the pool of cholesterol available for esterification by the acylCoA:cholesterol acyl transferase (ACAT) reaction. We evaluated whether this activity was associated with the presence of CAD and the risk of MACE and death during a 4.5-year follow-up. Serum-induced changes in ACAT activity did not correlate with HDL levels or the presence of CAD. Patients in the highest tertile of change in ACAT activity had a significantly higher risk for MACE (HR, 2.15; 95% CI, 1.36 to 3.39; P=0.001) and death (HR, 2.23; 95% CI, 1.17 to 4.26; P=0.01). These correlations were independent of other risk markers including LDL, HDL, and C-reactive protein levels.
Conclusions:
Serum-induced depletion of cellular cholesterol available for esterification by ACAT was a strong, independent predictor of MACE and death. We speculate that the ability of serum to decrease ACAT activity depends on ATP binding cassette transporter A1 (ABCA1)-mediated efflux. Furthermore, serum samples that induce larger changes in ACAT activity contain increased levels of HDL particles that preferentially interact with ABCA1 and that these particles accumulate in the serum of patients because of low activity of ABCA1 in vivo preventing or limiting the extent of apoA-I lipidation.
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