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inducible expression in cultured neonatal
light chain 2 expression in the primitive
murine heart tube. Proc Natl Acad Sci USA
Zou Y, Chien KR: 1995. EFIA/YB-1 is a com-
Zammit PS, Kelly RG, Franco D, et al.: 2000.
and positively regulates transcription of
Suppression of atrial myosin gene expres-
the myosin light chain-2 v gene. Mol Cell
ventricular specificity and establishes an
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anterior-posterior gradient of expression.
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Platelets are blood cell fragments that originate from the cytoplasm of
megakaryocytes in the bone marrow and circulate in blood to play a
major role in the hemostatic process and in thrombus formation after
an endothelial injury. Recent studies have provided insight into platelet
mRNA distribution patterns in the rat heart.
Cardiovasc Res 32:886 – 900.
functions in inflammation and atherosclerosis. A range of molecules,
present on the platelet surface and/or stored in platelet granules, con-
tributes to the cross-talk of platelets with other inflammatory cells
during the vascular inflammation involved in the development and
& N Rosenthal (Eds.), Heart development( pp. 357 – 369). San Diego, CA: Academic
progression of atherosclerosis. This review discusses the nature of these
molecules and the mechanisms involved in the participation of plate-
Wang GF, Nikovits W, Schleinitz M, Stock-
lets in atherosclerosis, with emphasis on P-selectin, platelet–monocyte
dale FE: 1998. Atrial chamber-specific ex-
interactions, chemokines, and inflammatory cytokines. (Trends
pression of the slow myosin heavy chain 3gene in the embryonic heart. J Biol Chem
Cardiovasc Med 2004;14:18–22) n 2004, Elsevier Inc.
Wang GF, Nikovits W Jr, Schleinitz M, Stock-
dale FE 2001. A positive GATA element and
a negative vitamin D receptor-like element
Cardiovascular Research Center and Depart-
control atrial chamber-specific expression
ment of Biomedical Engineering, University
of Virginia, Health Science Center, Charlot-
tection of activated platelets as defined
diovascular Research Center and Department
Wang GF, Nikovits W Jr, Bao ZZ, Stockdale
FE: 2003. Irx4 forms an inhibitory complex
Virginia, Health Science Center, Box 801394,
atherosclerotic disease was first reported
Charlottesville, VA 22908, USA. Tel.: (+1) 434-
tors to regulate cardiac chamber-specific
by Fitzgerald et al. (1986). These circu-
243-9351; fax: (+1) 434-924-2828; e-mail:
lating activated platelets are very likely
to associate with thrombotic events. Cir-
D 2004, Elsevier Inc. All rights reserved.
findings did not support a beneficial ef-
fect of aspirin in atherosclerosis (Cayatte
et al. 2000, Napoli et al. 2002). Also, the
et al. 1998). Interestingly, most risk fac-
inhibitory effect of aspirin in atheroscle-
tors of atherosclerosis—including hyper-
cholesterolemia (Broijersen et al. 1998),
smooth muscle cells in the vessel wall.
vated platelets in circulation. The pres-
platelets transiently interacting with the
ble for platelet activation in atherosclero-
A23187 (Frenette et al. 1995). Consistent
platelet activation begins with the bind-
ing of adhesive receptors to their ligands
bution of platelet – endothelial inter-
but robustly with atherosclerotic carotid
facilitate the delivery of platelet-derived
et al. 2003). These interactions are main-
let – endothelial interactions in the devel-
and stimulated platelets, epinephrine re-
(Huo et al. 2003). Platelet P-selectin is
important. Repeated injections of P-selec-
phase of atherosclerosis, platelet activa-
lial ligand for platelet P-selectin is un-
mice accelerated the formation of athero-
sclerotic lesions (Huo et al. 2003). Recon-
of atherosclerosis, including superoxide,
for platelet translocation and firm adhe-
control mice (Burger and Wagner 2003).
sion, respectively. In addition to P-selec-
atherosclerosis is controversial. In pigs
ecule in both resting and activated plate-
sites of arteries of rabbits with hypercho-
1980, Nichols et al. 1998). Deficiency of
et al. 2002) also found GPIIb/IIIa-mediat-
did not show any protective role in devel-
ditionally, following formation of lesions
opment of atherosclerosis (Sramek et al.
on the vessel wall, platelet activation may
be initiated by ligation of GPIb with the
definitions of firm adhesion are likely to
influence the results. Consistent with the
Platelet activation influences the devel-
deficient in VWF have a defect in secretion
an injection of in vitro activated platelets.
bodies. Thus, endothelial P-selectin-medi-
in these VWF mutant mice (Denis et al.
luminal surfaces of atherosclerotic arter-
conflicting data exist. For example, some
or avidity of monocyte/leukocyte integ-rins via P-selectin glycoprotein ligand-1(PSGL-1) signaling or delivery of plate-let-derived proinflammatory factors(Figure 1B). Oxidative burst occurs onmonocytes in response to platelet bind-ing. These rapid platelet-mediated regu-lations may play a role in atherosclerosisby promoting monocyte recruitment(Figure 1B). Activated platelets are alsoable to cause a variety of slow reactions.
Resting monocytes do not express tissuefactor, a protein involved in the initia-tion of blood coagulation and the forma-tion of atherosclerotic lesions. However,upon interaction with platelet P-selectin,
Figure 1. Mechanisms by which activated platelets participate in the development ofatherosclerosis. (A) No interactions occur between resting platelets and monocytes. (B)
transcription of tissue factor is activated.
Activated platelets promote monocyte recruitment via platelet – monocyte interactions.
Activated platelets interacting with monocytes deliver their proinflammatory factors to
monocytes. Consequently, affinity and/or avidity of monocyte integrins are upregulated and
monocytes arrest on endothelium. Additionally, monocyte – platelet aggregates may employ
platelet P-selectin to mediate aggregates to interact with endothelium. (C) Activated platelets
promote monocyte recruitment via platelet – endothelial interactions. Activated platelets
transiently interacting with endothelium may deposit their proinflammatory factors on thesurface of endothelium, causing subsequent rolling monocyte arrest. Also, platelet-derived
proinflammatory factors may infiltrate into the vessel wall, triggering vascular cell prolifer-
are primed by several different synergis-
tic activators. Exposure of monocytes toplatelet P-selectin and platelet activating
factor mobilizes the transcription factor
bound to activated GPIIb/IIIa complex.
a ligand for leukocyte Mac-1 (Simon et al.
platelet – leukocyte aggregates are not
sclerosis (Shpilberg et al. 2002). This is
Michelson et al. (2001) found that the life
crete a different set of cytokines, includ-
mice. In atherosclerotic mice, deficiency
shedding. In our in vivo study (Huo et al.
2003), 2 to 3 hours after an injection of
activated platelets, circulating platelet –
tectable and ‘‘normal’’ leukocyte subtype
tions between monocytes and platelets.
P-selectin on activated platelets initiates
their interactions with leukocytes. Among
leukocyte subtypes interacting with acti-
shed their P-selectin (Berger et al. 1998),
vated platelets, monocytes have a compet-
suggesting that most platelet – leukocyte
activated platelets (Huo et al. 2003). The
sequester into peripheral tissues or mono-
tially bind platelets, a possible basis for
cytes phagocytose platelets bound to their
the role of activated platelets in the devel-
opment of atherosclerosis, is unknown.
ly, interactions between activated plate-
lets and leukocytes will be stabilized due
to binding of leukocyte integrins to plate-
telets are able to upregulate affinity and/
ces that are contained within the a gran-
of inflammatory reactions, as do activat-
sclerotic lesions, direct evidence is need-
ed platelets. The role of activated platelets
are endocytosed from the blood plasma.
in atherosclerotic lesions is really ‘‘plate-
rosis. Platelet factor 4 (PF-4), a member
derived by limited proteolysis from plate-
let basic protein. PF-4 causes chemotaxis
lets have recently received intense inter-
Thirty years after Ross et al. (1976) pro-
cent studies (Nassar et al. 2003) provide
protein of the TNF family originally iden-
atherosclerosis, direct evidence now sup-
4 in the development of atherosclerosis.
telets truly play an important role in the
platelets in atherosclerosis, although par-
tially suggested in primary studies, have
cleaved over a period of minutes or hours,
generating a soluble but functional frag-
rived foam cells, is able to dramatically
capable of initiating various inflammato-
ment and progression of atherosclerosis.
ry responses on endothelial cells, includ-
ing production of reactive oxygen species
(Urbich et al. 2002), expression of adhe-
et al. 2003, Sachais et al. 2002). RANTES
sion molecules (e.g., vascular cell adhe-
sion molecule 1, ICAM-1, and E-selectin),
factor (Slupsky et al. 1998). In contrast to
preparation of this manuscript. This work
sented in its mature form on the platelet
arteries, suggesting that platelet-derived
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NEW ITEMS IN THE NBMA RESOURCE LIBRARY Super bugs Dec. 2009/Jan. 2010 TITLE: Occurrence of antibiotic-resistant bacteria and endotoxin associated with the land application of biosolids Author: Brooks, J.P., S.L. Maxwell, C. Rensing, C.P. Gerba, and I.L. Pepper Source: Can. J. Microbiol. 2007 53:616-622 Abstract: The purpose of this study was to determine the prevalence of antib
Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000158445.68149.38 A PROSPECTIVE, RANDOMIZED, PLACEBO CONTROLLED, DOUBLE-BLIND STUDY OF PELVIC ELECTROMAGNETIC THERAPY FOR THETREATMENT OF CHRONIC PELVIC PAIN SYNDROME WITH 1 YEAR OFE. ROWE, C. SMITH, L. LAVERICK, J. ELKABIR, R. O’N WITHEROW AND A. PATEL From the Department of Urology, St. Mary’s Hospital, London