期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 109, 期 8, 页码 1031-1040出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI200210649
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资金
- AHRQ HHS [HS-41460] Funding Source: Medline
- Intramural NIH HHS [Z01 NS002038] Funding Source: Medline
- NHLBI NIH HHS [P01 HL046403, HL-59488, T32 HL007423, HL-69448, R01 HL069448, R01 HL047073, HL-46403, R01 HL059488, R37 HL047073, HL-07423, HL-47073] Funding Source: Medline
- NINDS NIH HHS [NS-02038, R01 NS041460] Funding Source: Medline
Endothelial CD39 metabolizes ADP released from activated platelets. Recombinant soluble human CD39 (solCD39) potently inhibited ex vivo platelet aggregation in response to ADP and reduced cerebral infarct volumes in mice following transient middle cerebral artery occlusion, even when given 3 hours after stroke. Postischemic platelet and fibrin deposition were decreased and perfusion increased without increasing intracerebral hemorrhage. In contrast, aspirin did not increase postischemic blood flow or reduce infarction volume, but did increase intracerebral hemorrhage. Mice lacking the enzymatically active extracellular portion of the CD39 molecule were generated by replacement of exons 4-6 (apyrase-conserved regions 2-4) with a PGKneo cassette. Although CD39 mRNA 3' of the neomycin cassette insertion site was detected, brains from these mice lacked both apyrase activity and CD39 immunoreactivity. Although their baseline phenotype, hematological profiles, and bleeding times were normal, cd39(-/-) mice exhibited increased cerebral infarct volumes and reduced postischemic perfusion. solCD39 reconstituted these mice, restoring postischemic cerebral perfusion and rescuing them from cerebral injury. These data demonstrate that CD39 exerts a protective thromboregulatory function in stroke.
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