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Circulation. 2005;111:381

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(Circulation. 2005;111:381.)
© 2005 American Heart Association, Inc.

Issue Highlights


*    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.


*    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.


*    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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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.Down



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Correspondence
See p e37.


Related Articles:

Fibroblasts Can Be Genetically Modified to Produce Excitable Cells Capable of Electrical Coupling
Eddy Kizana, Samantha L. Ginn, David G. Allen, David L. Ross, and Ian E. Alexander
Circulation 2005 111: 394-398. [Abstract] [Full Text]

Short-Term Treatment With Atorvastatin Reduces Platelet CD40 Ligand and Thrombin Generation in Hypercholesterolemic Patients
Valerio Sanguigni, Pasquale Pignatelli, Luisa Lenti, Domenico Ferro, Alfonso Bellia, Roberto Carnevale, Manfredi Tesauro, Roberto Sorge, Renato Lauro, and Francesco Violi
Circulation 2005 111: 412-419. [Abstract] [Full Text]

Transforming Growth Factor-ß Receptor Mutations and Pulmonary Arterial Hypertension in Childhood
Rachel E. Harrison, Rolf Berger, Sheila G. Haworth, Robert Tulloh, Christoph J. Mache, Nicholas W. Morrell, Micheala A. Aldred, and Richard C. Trembath
Circulation 2005 111: 435-441. [Abstract] [Full Text]

How to Make Sure the Beat Goes On: Protecting a Woman’s Heart
Paula A. Johnson and JoAnn E. Manson
Circulation 2005 111: e28-e33. [Full Text]

High Left Ventricular Assist Device Flows Resulting From Combined Native Aortic Valve and Outflow Valve Regurgitation
Offer Amir, Biswajit Kar, Reynolds M. Delgado, III, Antoine G. Younis, Igor D. Gregoric, Frank W. Smart, Branislav Radovancevic, and O.H. Frazier
Circulation 2005 111: e34. [Full Text]

Left Ventricular Pseudoaneurysm: Echocardiographic and Intraoperative Images
Demetrio Tallarico, Pier Andrea Chiavari, Pasquale Mollo, and Giuseppe Campolongo
Circulation 2005 111: e35-e36. [Full Text]

Letter Regarding Article by Mozaffarian et al, "Fish Intake and Risk of Incident Atrial Fibrillation" Response
Jeppe Hagstrup Christensen, Erik Berg Schmidt, Egon Toft, Dariush Mozaffarian, Eric B. Rimm, Bruce M. Psaty, David S. Siscovick, Rozenn N. Lemaitre, Gregory L. Burke, Mary F. Lyles, and David Lefkowitz
Circulation 2005 111: e37. [Full Text]




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