Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy.

Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy. Research Abstract Details 

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Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy. Abstract Text:

Tong Tang,H Kirk Hammond,

Recent loss-of-function studies highlight the importance of the transcription factor GATA4 in the myocardial response to injury in the adult heart. However, the potential effects of gain-in-function of GATA4 overexpression, and transcription factors in general, is hindered by the fact that transcription factors are neither secreted nor taken up by cells. Chimeric proteins incorporating motifs of cell-penetrating proteins are secreted from cells and internalized by surrounding cells. We engineered a chimeric protein consisting of GATA4 and the cell-penetrating protein VP22. Cardiac fibroblasts stably transfected with the GATA4:VP22, GFP:VP22, or green fluorescent protein (GFP) constructs were transplanted into Lewis rats 1 month after left anterior descending ligation. GATA4:VP22 expression in the border zone was associated with increased cardiac myosin expression and cardiac myocyte size (30 mum versus 19 mum, P<0.01). Compared with the GFP:VP22 control group, 6 weeks after cardiac fibroblast transplantation (10 weeks after myocardial infarction), animals that received GATA4:VP22-expressing cardiac fibroblasts demonstrated increased cardiac function and less negative remodeling. These data demonstrate a novel strategy for transcription factor delivery to injured myocardium and indicate that the delivery of GATA4 locally to the infarct border zone induces multiple local effects in the border zone cardiac myocytes resulting in beneficial ventricular remodeling and improved global left ventricular function.

Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy. Publishing Authors By Initials

T Tang,HK Hammond,

For similar proteins: viral proteins: viral structural proteins research abstracts see: proteins: viral proteins: viral structural proteins research

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Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Circulation research

VOLUME: 100

Page Numbers: 1626-33

Journal Abbreviation: Circ. Res.

ISSN: 1524-4571

DAY: 10

MONTH: 05

YEAR: 2007

Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 47103

Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy. Keywords Mesh Terms:

KEYWORDS: Viral Structural Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy. Information

Substance Name: Green Fluorescent Proteins

Registry Number: 147336-22-9

Grant and Affiliation Information for Effect of cell-based intercellular delivery of transcription factor GATA4 on ischemic cardiomyopathy.

AFFILIATION: Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL74400

ACRONYM: HL

MEDLINETA: Circ Res

REFSOURCE: Circ Res. 2007 Jun 8;100(11):1540-2

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