Biomedical Engineering Reference
In-Depth Information
human cultured iliac vein ECs, and P-selectin mRNA expression was quantii ed.
h ey found that L-NAME caused increased expression of P-selectin mRNA. h e
stimulatory ef ect of L-NAME was reversed by the addition of L-Arg. h e ef ects
of the NO donor and L-Arg were also paralleled by decreases in P-selectin protein
synthesis and in decreased adherence of human neutrophils to human iliac venous
ECs. Another study investigated plasma NO levels and the expression of P-selectin
on platelets in preeclampsia. Studies were carried out in the third trimester of
normal pregnant women and women with preeclampsia. Also, the ef ects of the
inhibition of NO synthesis on the expression of P-selectin on platelets
in vitro
were
examined. h e results showed that nitrate levels and the expression of P-selectin
in preeclampsia were higher than those in a normal pregnancy. NO synthesis
inhibition
in vitro
signii cantly increased the expression of P-selectin in normal
pregnancy and preeclampsia. h e i ndings of that study were consistent with a
modulatory role of NO in dampening excessive platelet activation in normal
and preeclamptic pregnant women (Yoneyama
et al.
2002). However, an
in vitro
study performed by Beauvais
et al.
(1995) found that when human neutrophils
were placed in a gradient of an NO donor, directed locomotion was induced, as
evidenced by experiments of chemotaxis under agarose indicating that exogenous
NO elicits chemotaxis of neutrophils. An animal study investigating the ef ects of
NO on neutrophil sequestration in lung tissue found that endogenous NO might
have no association with the expression levels of L-selectin, P-selectin, or CD18 by
neutrophils (Roman and McGahren 2006). h e results of those studies mentioned
above suggest that NO has both pro- and anti-inl ammatory activities. Depending
on the levels produced, NO may be released to inl uence nearby cells or may act
as an intracellular messenger regulating the activity of cells responsible for its
generation. h e discrepancies between experiments dealing with the inhibition of
NOS versus exogenous application of NO-generating compounds may be partly
explained by localized versus widespread activities of NO.
POSSIBLE MECHANISMS OF NO IN REGULATING CAM
EXPRESSIONS
According to a study by Spiecker
et al.
(1997), the mechanisms by which NO
decreases endothelial and leukocyte adhesion molecule expressions possibly
occurs through inhibition of the pleiotropic transcription factor, nuclear factor-κB
(NF-κB). Previous studies suggested that NF-κB is required for the transcriptional
induction of EC adhesion molecules. h e activation of NF-κB involves the
degradation of its cytoplasmic inhibitor, IκB. At er administration of external
stimulants, including lipopolysaccharide and cytokines, IκB is phosphorylated.
Phosphorylation of IκB targets IκB for ubiquitination and rapid degradation. h e
degradation of IκB allows the unbound NF-κB to be translocated to the nucleus,
where it can transactivate the enhancer elements of many pro-inl ammatory genes.
