Abstract | OBJECTIVES: METHODS: We analyzed cardiac and brain cryosections for PAI-1 mRNA, as well as mRNAs encoding three receptor subunits, by in situ hybridization using 35S-labeled specific riboprobes. PAI-1 activity was tested in cardiac homogenates using one-phase reverse zymography. RESULTS: Prominent PAI-1 mRNA hybridization signals were induced in the vascular cells of the heart, and unexpectedly, also in cardiocytes, within 1-2 h after injection of kainate (i. p., 11-25 mg/kg body weight); the signals persisted for at least 8 h and disappeared after 24 h. In addition, PAI-1 activity increased ( approximately 5 fold) 2-10 h after the treatment. In contrast, mRNAs encoding the kainate/ AMPA receptor subunits could not be detected. The adrenergic agents adrenaline (3.5 mg/kg) and isoproterenol (200 mg/kg) exerted kainate-like effects in cardiovascular cells. CONCLUSIONS: These results revealed, for the first time, that PAI-1 gene expression can be enhanced locally in the cardiovascular system by a fast-acting neurological mechanism triggered by glutamate receptors, whose pathway and relation to catecholamines, which exerted similar effects, have yet to be resolved. These findings raised the possibility that excessive glutamate, or stress-related catecholamines, may increase the risk of stroke and myocardial infarction.
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Authors | B Venugopal, R Sharon, R Abramovitz, A Khasin, R Miskin |
Journal | Cardiovascular research
(Cardiovasc Res)
Vol. 49
Issue 2
Pg. 476-83
(Feb 01 2001)
ISSN: 0008-6363 [Print] England |
PMID | 11164858
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic Agonists
- Adrenergic beta-Agonists
- Excitatory Amino Acid Antagonists
- Plasminogen Activator Inhibitor 1
- RNA, Messenger
- Receptors, Glutamate
- Isoproterenol
- Kainic Acid
- Epinephrine
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Topics |
- Adrenergic Agonists
(pharmacology)
- Adrenergic beta-Agonists
(pharmacology)
- Animals
- Brain Chemistry
- Cardiovascular System
(metabolism)
- Electrophoresis, Polyacrylamide Gel
- Endothelium, Vascular
(chemistry, metabolism)
- Epinephrine
(pharmacology)
- Excitatory Amino Acid Antagonists
(pharmacology)
- Female
- In Situ Hybridization
- Isoproterenol
(pharmacology)
- Kainic Acid
(pharmacology)
- Mice
- Muscle, Smooth, Vascular
(chemistry, metabolism)
- Myocardium
(chemistry, metabolism)
- Plasminogen Activator Inhibitor 1
(genetics, metabolism)
- RNA, Messenger
(analysis)
- Receptors, Glutamate
(genetics, metabolism)
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