In man the haptoglobin (Hp) gene is polymorphic with two common alleles denoted 1
and 2 [
[1]
]. We have recently demonstrated in multiple independent longitudinal studies that
there is an up to 500% increase in the incidence of cardiovascular disease in individuals
with the Hp 2–2 genotype and diabetes mellitus (DM) [
2
,
3
,
4
,
5
,
6
]. The normal function of Hp is to bind extracorpuscular hemoglobin (Hb) and promote
its clearance after it is released into either the blood secondary to red cell intravascular
hemolysis (6 g per day in a normal man) or into the extravascular compartment after hemorrhage
(i.e., after hemorrhage into the atherosclerotic plaque) [
[1]
]. We and others have previously demonstrated that the Hp 1 allele protein product
is superior to the Hp 2 allele protein product in blocking Hb induced oxidation of
multiple substrates including LDL and HDL [
7
,
8
,
9
]. The major pathway for clearance of the Hp–Hb complex from the blood as well as from
the atherosclerotic plaque is via the monocyte/macrophage CD163 receptor [
[10]
]. We have demonstrated that the Hp 1–Hb complex is cleared more rapidly by the CD163
receptor than the Hp 2–Hb complex [
[11]
]. Furthermore, the amount of the CD163 receptor expressed on monocyte/macrophages
is decreased in Hp 2–2 and DM individuals [
[12]
]. In this study we set out to test the hypothesis that the Hp genotype regulates the
turnover and oxidative activity of Hb in the atherosclerotic plaque.To read this article in full you will need to make a payment
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Article info
Publication history
Received:
September 1,
2009
Identification
Copyright
© 2009 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
