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HERO ID
1525104
Reference Type
Journal Article
Title
Haptoglobin polymorphism affects nitric oxide bioavailability in preeclampsia
Author(s)
Sertório, JT; Lacchini, R; Amaral, LM; Palei, AC; Cavalli, RC; Sandrim, VC; Duarte, G; Tanus-Santos, JE
Year
2013
Is Peer Reviewed?
Yes
Journal
Journal of Human Hypertension
ISSN:
0950-9240
EISSN:
1476-5527
Volume
27
Issue
6
Page Numbers
349-354
Language
English
PMID
23223086
DOI
10.1038/jhh.2012.57
Web of Science Id
WOS:000318689400003
Abstract
Studies showed elevated cell-free hemoglobin (Hb) in preeclampsia (PE), and Hb reacts with nitric oxide (NO), decreasing its bioavailability. Haptoglobin (Hp) is a polymorphic protein (Hp1-1, Hp2-1 and Hp2-2) that binds Hb to form a complex that is removed from circulation, thus preventing Hb-driven oxidative stress and NO scavenging. Hp protein products differ in biochemical and biophysical properties, which reflects on the Hb-Hp complex clearance rate. We hypothesized that Hp phenotypes modulate NO bioavailability by influencing NO consumption in PE. We studied 92 PE subjects and 105 normal pregnant women (NP). Hp genotypes were determined using real-time PCR. To assess NO bioavailability, we measured plasma nitrite using an ozone-based chemiluminescence assay. Plasma Hb and Hp were assessed with commercial immunoassays. A NO consumption assay was used to measure NO consumption. We found no differences in Hp genotype frequencies between PE and NP groups. Hp genotypes had no effects on plasma heme levels, NO consumption and plasma nitrite in NP. However, in PE, Hp2-1 and Hp2-2 were associated with higher plasma heme levels (48 and 55% higher, respectively; P<0.05), increased NO consumption (42 and 44% more, respectively; P<0.05) and lower plasma nitrite (39% less for Hp2-2; P<0.05) compared with Hp1-1. These findings indicate that although Hp genotype does not affect the risk of PE, Hp1-1 genotype may exert a protective role in PE by reducing NO scavenging, whereas Hp2-1 and Hp2-2 further may aggravate PE by reducing NO bioavailability.Journal of Human Hypertension advance online publication, 6 December 2012; doi:10.1038/jhh.2012.57.
Keywords
haptoglobin; hemoglobin; hemolysis; nitric oxide; polymorphism; preeclampsia
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ISA-Ozone (2020 Final Project Page)
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