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Sci. Signal., 5 January 2010
Vol. 3, Issue 103, p. ra1
[DOI: 10.1126/scisignal.2000551]

RESEARCH ARTICLES

Editor's Summary

Aggregation Regulation
When damage occurs to the endothelium lining a blood vessel and exposes the underlying extracellular matrix, platelets adhere to the site of injury and aggregate to stop blood loss. However, aggregated platelets can cause ischemia if they occlude the vessel, thus creating the need for therapies that can limit platelet aggregation without increasing blood loss. Elvers et al. found that platelets from mice deficient in phospholipase D1 (PLD1) showed reduced activation of {alpha}IIbβ3 integrin, a major adhesion receptor, and did not form stable aggregates when experiencing high shear forces (such as those found in small arterioles). PLD1 deficiency conferred protection against thrombosis and cerebral ischemia in vivo, an effect that was seen with Pld1–/– mice and wild-type mice transplanted with bone marrow from Pld1–/– mice. PLD1 deficiency did not, however, increase blood loss after tail wounding. Thus, PLD1 could be a potential therapeutic target to prevent or treat stroke or other ischemic conditions.

Citation: M. Elvers, D. Stegner, I. Hagedorn, C. Kleinschnitz, A. Braun, M. E. J. Kuijpers, M. Boesl, Q. Chen, J. W. M. Heemskerk, G. Stoll, M. A. Frohman, B. Nieswandt, Impaired {alpha}IIbβ3 Integrin Activation and Shear-Dependent Thrombus Formation in Mice Lacking Phospholipase D1. Sci. Signal. 3, ra1 (2010).

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