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Ccm1 Assures Microvascular Integrity During Angiogenesis

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Abstract

Cerebral cavernous malformations (CCM) are characterized by abnormal dilated intracranial capillaries that predispose to hemorrhage. The development of some CCMs in humans has been attributed to mutations in the CCM1 genes. Currently, contradictory results have been generated regarding the vascular endothelial cell population changes in Ccm1 deficiency in zebrafish. We hypothesize that the inconsistent results simply reflect the spatial and temporal difference for the observed vascular endothelial cells during zebrafish embryonic development. Using high resolution images in vivo, we demonstrated that the loss of Ccm1 in zebrafish embryos leads to marked increases in apoptosis in vascular endothelium at the end stage of microvascular angiogenesis. In vivo zebrafish studies were further substantiated by in vitro findings in human endothelial cells that elucidated the biochemical pathways of CCM1 deficiency. We found that that loss of CCM1 in vitro promotes apoptosis through decreased activation of the integrin-linked kinase survival signaling pathway. In summary, Ccm1 has been identified as a key modulator in maintaining microvascular integrity during zebrafish embryonic angiogenesis.

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Acknowledgments

We thank Chris Carr and Betty Chen at UMMC Neurosurgery, Hal Dietz, Richard Clatterbuck, and Sharmila Basu at Johns Hopkins University for their invaluable technical help and discussion during the experiments and in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Huiling Liu

  2. Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Daniele Rigamonti

  3. COE for Neurosciences, Departments of Anesthesiology, Biomedical Sciences, Neurosurgery, Texas Tech University Health Science Center, 4800 Alberta Avenue, El Paso, TX, 79905, USA

    Ahmed Badr & Jun Zhang

Authors
  1. Huiling Liu
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  2. Daniele Rigamonti
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  3. Ahmed Badr
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  4. Jun Zhang
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Correspondence to Jun Zhang.

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Liu, H., Rigamonti, D., Badr, A. et al. Ccm1 Assures Microvascular Integrity During Angiogenesis. Transl. Stroke Res. 1, 146–153 (2010). https://doi.org/10.1007/s12975-010-0010-z

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  • DOI: https://doi.org/10.1007/s12975-010-0010-z

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