Circulation. 2005;111:381
(Circulation. 2005;111:381.)
© 2005 American Heart Association, Inc.
Issue Highlights
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FIBROBLASTS CAN BE GENETICALLY MODIFIED TO PRODUCE EXCITABLE CELLS CAPABLE OF ELECTRICAL COUPLING, by Kizana et al.
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Genetic engineering to restore or create electrically excitable
tissue is being developed as a possible treatment for arrhythmias.
To attempt creation of electrical excitability in fibroblasts,
myogenesis was forced through expression of a skeletal myogenic
determination factor. Cells formed myotubes and expressed muscle-specific
proteins. Calcium transients were demonstrable in response to
electrical stimulation, indicating likely expression of ion
channels needed for excitability and calcium release; however,
there was no evidence of electrical coupling between myotubes.
In cultured cells that were also transduced with a connexion
43–containing vector dye, transfer studies confirmed communication
between myotubes, consistent with formation of gap junctions.
Electrical coupling was demonstrated in 15% of excitable adjacent
myotubes, indicated by an identical stimulus threshold for calcium
transients in the two coupled myotubes. These findings support
the feasibility of creating genetically engineered cells for
conduction of electrical impulses that could lead to cell-based
therapy for arrhythmias. See p
394.
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SHORT-TERM TREATMENT WITH ATORVASTATIN REDUCES PLATELET CD40 LIGAND AND THROMBIN GENERATION IN HYPERCHOLESTEROLEMIC PATIENTS, by Sanguigni et al.
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In patients at risk for coronary heart disease, treatment with
HMG-CoA reductase inhibitors (statins) is uniformly associated
with a reduction in subsequent cardiovascular events. The magnitude
of risk reduction as compared with other lipid-lowering therapies
has prompted considerable speculation that statins possess salutory
effects distinct from reductions in LDL cholesterol. In this
issue of
Circulation, Sanguigni and colleagues have found that
statin treatment has important implications for thrombosis.
In particular, hypercholesterolemic patients treated with HMG-CoA
reductase inhibition demonstrated reduced platelet CD40 ligand
content and in vivo thrombin generation. This effect was observed
before any observed reductions in LDL cholesterol. These observations
suggest that one "pleiotropic" effect of statin treatment is
to inhibit platelet-mediated thrombosis and that this effect
is quite rapid. See p
412.
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TRANSFORMING GROWTH FACTOR-ß RECEPTOR MUTATIONS AND PULMONARY ARTERIAL HYPERTENSION IN CHILDHOOD, by Harrison et al.
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Presentation of pulmonary artery hypertension (PAH) in early
life may be associated with congenital heart disease but is
frequently idiopathic. Harrison and colleagues performed mutational
analysis of genes encoding receptor members of the TGF-ß
cell-signaling pathway in 18 children with PAH. Mutations were
identified in 4 of 18 subjects (22%); these included mutations
in
BMPR2 (n=2),
ALK-1 (n=1) and
endoglin (n=1). Thus, diverse
genetic defects of the TGF-ß pathway may have a critical
role in the etiology of PAH presenting in childhood. These findings
have important implications for the investigation and management
of families presenting with very-early-onset PAH and suggest
that at least in some patients, PAH is associated with an inherited
developmental defect of the pulmonary vasculature. See p
435.
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Visit www.circ.ahajournals.org:
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Cardiology Patient Page
How to Make Sure the Beat Goes On: Protecting a Woman’s
Heart. See p
e28.
Images In Cardiovascular Medicine
High Left Ventricular Assist Device Flows Resulting From Combined Native Aortic Valve and Outflow Valve Regurgitation. See p e34.
Left Ventricular Pseudoaneurysm: Echocardiographic and Intraoperative Images. See p e35.
Correspondence
See p e37.
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