Determining the in vitro level of foam cell formation in different South African populations
Date
2018
Authors
Ralefatane, Maile George
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Abstract
Aim: A critical event in atherosclerosis is the accumulation of oxidised ( ox) LDL-laden foam
cells (FCs) derived from macrophages within the arterial wall. Macrophages are transformed
to FCs by the uptake of oxLDL by scavenger receptors i.e. MSR-1, CD36 and CD68.
Atherosclerosis differs in prevalence across genders (more common in males) and ethnic
groups (less common in African than Asian-Indian or European populations). Therefore, the
aim of this study was to compare FC formation across genders and ethnicities to determine if
gender and ethnic differences in the prevalence of atherosclerotic diseases are mirrored by
similar differences in the level of in vitro FC formation.
Methods: Forty one subjects were recruited into 2 groups; a younger group (n= 11; 7 African,
4 European) and an older group (n=30; ten from each of the 3 ethnic groups; 15 males and 15
females). Anthropometry and fasting lipid and glucose levels were measured. Monocytes were
isolated from whole blood and converted to macrophages and FCs using standard cell culture
procedures. The level of FC formation was determined by measuring intra-cellular lipid
accumulation (ICLA) using the lipid-specific dye Oil red 0. Macrophage expression of
scavenger receptors (MSR-1, CD36, CD68) was measured by quantitative rtPCR.
Results: The ICLA in macrophages exposed to oxLDL (measured as a % of ICLA in
unexposed cells) was significantly higher in the older (151.1 ± 27.9%) than the younger group
(99.9 ± 22.1 %; p=0.0001 ). No differences in macrophage ICLA were observed between ethnic
groups (African, 156.8 ± 28.1 %; European, 155.9 ± 57.9%; Indian, 136.8 ± 22.2%; p=0.42) or
genders (males, 158.8 ± 48.5%; females; 140.9 ± 25.3%; p=0.24). The expression of all
scavenger receptors changed minimally during foam cell formation and did not reflect the
gender and ethnic differences in the prevalence of atherosclerosis. Baseline (before addition of
oxLDL) macrophage expression levels of CD36, CD68 and MSRl correlated positively with
iv
serum LDL-C (p<0.05 for MSRl and CD36) and triglyceride levels (p=0.005; CD68 only),
and negatively with HDL-C (p=0.003; MSRl only).
Conclusions: This study shows that older subjects have a higher level of foam cell formation,
which may relate to their higher level of atherosclerosis. Gender and ethnic differences in foam
cell formation were not observed; whilst expression levels of scavenger receptors did not mimic
the gender and ethnic differences observed in the prevalence of atherosclerosis. This suggests
that in vitro foam cell formation does not mirror in vivo formation or that gender and ethnic
differences in the prevalence of atherosclerosis are not due to similar differences in foam cell
formation. The small effect of oxLDL on scavenger receptor expression suggests that
scavenger receptor levels may increase before foam cell formation occurs i.e. during the
transformation from monocytes to macrophages. The relationships observed between serum
lipid levels and basal scavenger receptor expressions are novel and may reflect an ability of
serum lipids to modulate scavenger receptor expression in macrophages even before exposure
to oxLDL.
Description
A dissertation submitted in fulfilment of the requirements for the degree of Master of Science in Medicine to the Faculty of Health Sciences, University
of the Witwatersrand, Johannesburg, 2018