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  • Donor-specific anti-HLA antibody production following pediatric ABO-incompatible heart transplantation PEDIATRIC TRANSPLANTATION Chen, C., Warner, P., Albers, E. L., Kemna, M. S., Delaney, M., Hong, B. J., Law, Y. M. 2019; 23 (2)

    View details for DOI 10.1111/petr.13332

    View details for Web of Science ID 000459211900010

  • Blood flow reprograms lymphatic vessels to blood vessels JOURNAL OF CLINICAL INVESTIGATION Chen, C., Bertozzi, C., Zou, Z., Yuan, L., Lee, J. S., Lu, M., Stachelek, S. J., Srinivasan, S., Guo, L., Vincente, A., Mericko, P., Levy, R. J., Makinen, T., Oliver, G., Kahn, M. L. 2012; 122 (6): 2006–17

    Abstract

    Human vascular malformations cause disease as a result of changes in blood flow and vascular hemodynamic forces. Although the genetic mutations that underlie the formation of many human vascular malformations are known, the extent to which abnormal blood flow can subsequently influence the vascular genetic program and natural history is not. Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic identity and expressed a marker of blood vessel identity. Genetic lineage tracing demonstrated that this change in vessel identity was the result of lymphatic endothelial cell reprogramming rather than replacement by blood endothelial cells. Exposure of lymphatic vessels to blood in the absence of significant flow did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly lost expression of PROX1, a lymphatic fate-specifying transcription factor. These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow.

    View details for DOI 10.1172/JCI57513

    View details for Web of Science ID 000304736300011

    View details for PubMedID 22622036

    View details for PubMedCentralID PMC3366395

  • Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling BLOOD Bertozzi, C. C., Schmaier, A. A., Mericko, P., Hess, P. R., Zou, Z., Chen, M., Chen, C., Xu, B., Lu, M., Zhou, D., Sebzda, E., Santore, M. T., Merianos, D. J., Stadtfeld, M., Flake, A. W., Graf, T., Skoda, R., Maltzman, J. S., Koretzky, G. A., Kahn, M. L. 2010; 116 (4): 661–70

    Abstract

    Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.

    View details for DOI 10.1182/blood-2010-02-270876

    View details for Web of Science ID 000280502800025

    View details for PubMedID 20363774

    View details for PubMedCentralID PMC3324297

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