A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model.

A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model. Research Abstract Details 

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A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model. Abstract Text:

Piotr Witkowski,Tetsunori Seki,Guosheng Xiang,Timothy Martens,Hugo Sondermeijer,Fiona See,Govind Bhagat,Michael Schuster,Mark A Hardy,Silviu Itescu,

We investigated whether targeted cleavage of PAI-1 mRNA might prevent post-angioplasty neointima formation in diabetic JCR:LA-cp/cp rats with naturally elevated PAI-1 levels. Catalytic DNA enzymes targeting rat PAI-1 mRNA (PAI-1 DNA enzyme, n = 12) or a random sequence as control (scrambled DNA enzyme, n = 12) were infused at the site of arterial damage. Control animals demonstrated prominent PAI-1 protein expression in the arterial endothelium at 48 hours, and robust neointimal proliferation by two weeks, with 60 +/- 10% mean occlusion of the artery lumen. The neointimal lesion consisted of dense fibrin deposition and numerous proliferating smooth muscle cells, as determined by dual alpha-smooth muscle actin/Ki67 expression. Treatment with PAI-1 DNA enzyme resulted in marked early (48 hour) reduction of endothelial PAI-1 protein expression, which persisted for the next two weeks as well as a two fold reduction of expression of PAI-1 mRNA by RT-PCR at the same time point, (P < 0.05). By two weeks, PAI-1 DNA enzyme treated animals demonstrated significantly reduced levels of fibrin deposition and 5-fold lower levels of proliferating smooth muscle cells at the site of arterial injury compared to controls (P < 0.01), and a 2-fold lower neointima/media ratio (0.67 +/- 0.11 vs 1.39 +/- 0.12) (P < 0.05). Treatment with a catalytic PAI-1 DNA enzyme successfully prevents neointimal proliferation after balloon injury in diabetic animals.

A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model. Publishing Authors By Initials

P Witkowski,T Seki,G Xiang,T Martens,H Sondermeijer,F See,G Bhagat,M Schuster,MA Hardy,S Itescu,

For similar cardiovascular system: blood vessels: endothelium, vascular: tunica intima research abstracts see: cardiovascular system: blood vessels: endothelium, vascular: tunica intima research

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A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of cardiovascular pharmacology

VOLUME: 50

Page Numbers: 633-40

Journal Abbreviation: J. Cardiovasc. Pharmacol.

ISSN: 0160-2446

DAY: 27

MONTH: Dec

YEAR: 2007

A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model. Information

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LANGUAGE: eng

NlmUniqueID: 7902492

A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model. Keywords Mesh Terms:

KEYWORDS: Tunica Intima

MESH TERMS: pathology

Chemical & Substance for Abstract: A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model. Information

Substance Name: Fibrin

Registry Number: 9001-31-4

Grant and Affiliation Information for A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model.

AFFILIATION: Department of Surgery, Columbia University, College of Surgeons and Physicians, New York, New York, USA. pw2004@columbia.edu

Country: United States

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MEDLINETA: J Cardiovasc Pharmacol

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