Abstract
Background
Atherosclerosis involves the accumulation of oxidized low-density lipoprotein (OxLDL)-laden foam cells (FC) within the blood vessel intima. Macrophages are transformed to FCs by the uptake of OxLDL, a process mediated by scavenger receptors (SRs), which include MSR1, CD36 and CD68. Atherosclerosis differs in prevalence across ethnic groups, being less common in African than Indian or European populations. Therefore, our aim was to measure SRs gene expression from macrophages isolated from these three ethnic groups.
Methods
Ten participants were recruited from each ethnic group (African, European and Indian). Anthropometry and fasting serum lipid and glucose levels were measured. Monocytes were isolated from whole blood and converted to macrophages using standard cell culture procedures. Macrophage RNA was isolated, and reverse transcribed to cDNA. Relative gene expression was calculated using the ∆∆Ct relative quantification method with β-actin used as the normalization control. Multivariable regression analysis was performed to identify the determinants of macrophage SRs expression.
Results
Expression of the CD36 gene correlated with age (β = 0.33, p = 0.02), LDL (β = 0.29, p = 0.03) and CD68 expression (β = 0.57, p < 0.001). Expression of CD68 correlated with triglycerides (β = 0.45, p = 0.005) and European ethnicity (β = 0.56, p < 0.001). Expression levels of MSR1 correlated positively with LDL (β = 0.27, p = 0.01) and negatively with HDL (β=-0.33, p = 0.003) and African ethnicity (β=-0.73, p < 0.001).
Conclusions
These data suggest that serum lipids may modulate foam cell formation via effects on macrophage SRs gene expression. Furthermore, ethnic differences in atherosclerotic plaque formation may be mediated through differential CD68 and MSR1 expression levels within macrophages.
TRAIL/DR5 Signaling Promotes Macrophage Foam Cell Formation by Modulating Scavenger Receptor Expression
