CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 1, February 2012
26
AFRICA
ferritin being an inflammatory marker, we found a significant
positive correlation between ferritin and nitric oxide levels.
Stimulation of macrophages with interferon and lipopolysac-
charides induced NO synthesis and activated iron regulatory
protein (IRP) binding by IRP 1 and 2. The regulatory cross talk
between iron metabolism and NO was further highlighted by the
transcriptional regulation of the inducible NO synthase gene by
iron.
26
Our results confirm those of other studies, which showed
that inflammation and inflammatory cytokines, which are known
to stimulate NO production, stimulated ferritin synthesis.
27
Another highlight of our study was detecting hyperapoli-
poproteinaemia in the CAD patients. The Quebec Heart study
demonstrated accelerated CAD in patients with hyperapolipo-
proteinaemia B.
28
In a study conducted by Genest
et al
. in 321
men, it was observed that the level of apolipoprotein B was
increased and that of apolipoprotein A decreased in myocardial
infarction patients.
29
A highly significant positive correlation
between ferritin and apolipoprotein B levels was observed
in our study population. Apolipoprotein B levels signify the
extent of dyslipidaemia. The positive correlation between these
two parameters throws some light on the complex interaction
between inflammation and dyslipidaemia in the pathogenesis of
atherosclerosis and its ultimate clinical manifestation, namely
acute coronary syndrome, which includes myocardial infarction.
The most typical change in lipoprotein metabolism during
infection and inflammation is hypertriglyceridaemia. In addition
to the observed changes in LDL-C levels, a change in LDL size
and their susceptibility to oxidation was also noticed. Enhanced
LDL oxidation has been documented during infection and
inflammation. Moreover there were reductions in the plasma
proteins proposed to play a major role in HDL metabolism and
reverse cholesterol transport, including lecithin, cholesterol acyl
transferase (LCAT), cholesterol ester transport protein (CETP),
hepatic lipase (HL) and phospholipid transfer protein (PLTP).
Because of these changes in HDL metabolism, it was postulated
that the main function of HDL, namely its role in protecting LDL
against oxidation and reverse cholesterol transport (RCT) may be
decreased in acute-phase responses (APR).
30,31
In the present study we found that dyslipidaemia correlated
positively with NO concentration. Peroxynitrite, formed by the
reaction of NO with free radicals, triggers lipid peroxidation
in membranes
32
and lipoproteins by removing a hydrogen atom
from polyunsaturated fatty acids (PUFA), leading to the forma-
tion of lipid hydroperoxyradicals, conjugated dienes and alde-
hydes.
33
One study demonstrated that in older patients, the immu-
noreactivity of NO was found in close association with foam
cells, vascular endothelium and in the neo-intima of advanced
atherosclerotic lesions.
34
Peroxynitrite-modified LDL also binds with high affinity to
scavenger receptors and leads to the accumulation of oxidised
cholesteryl esters and foam cell formation, which is a key early
event in atherogenesis.
35,36
Another study demonstrated that
reactive nitrogen species generated by the myeloperoxidase/
hydrogen peroxide/nitrite system of monocytes converted LDL
to a form (NO
2
-LDL) that was readily taken up and degraded
by macrophages, leading to massive cholesterol deposition and
foam cell formation.
37
Atherosclerosis is now known to be associated with multiple
aetiologies: oxidative stress, dyslipidaemia, inflammation and
other novel risk factors. These interact at the molecular level
in a highly complex manner to influence the entire process of
atherogenesis.
The main limitation of our study was the lack of follow-
up data due to lack of patient compliance and administrative
constraints. A large-scale prospective study with follow-up data
would facilitate our understanding of the present perspective on
CAD in India.
Conclusion
Our study highlights the interplay between ferritin, NO and
apolipoprotein B levels. The ever-increasing knowledge on the
various risk factors and molecular mechanisms underlying CAD
calls for a critical appraisal of the existing understanding and
shortcomings in order to better manage this pandemic.
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