國家衛生研究院 NHRI:Item 3990099045/6697
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    题名: beta2-integrin and notch-1 differentially regulate CD34+CD31+ cell plasticity in vascular niches
    其它题名: β2-integrin and notch-1 differentially regulate CD34+CD31+ cell plasticity in vascular niches
    作者: Shih, YT;Wang, MC;Yang, TL;Zhou, J;Lee, DY;Lee, PL;Yet, SF;Chiu, JJ
    贡献者: Division of Medical Engineering Research;Institute of Cellular and Systems Medicine
    摘要: AIMS: The implication of circulating hematopoietic CD34(+) progenitors in vasculature is hampered by the incomprehension on their characterization and plasticity mediated by their cellular microenvironment. We investigated how vascular smooth muscle cells (SMCs) and their interactions with endothelial cells (ECs) affect the behavior and plasticity of CD34(+)CD31(+) progenitors and the underlying mechanisms. METHODS AND RESULTS: Human peripheral blood-derived CD34(+)CD31(+) cells were directly transplanted into injured arteries in vivo and co-cultured with ECs and SMCs in vitro. CD34(+)CD31(+) progenitors injected into wire-injured mouse arteries differentiated into ECs and macrophages in the neoendothelial layer and neointima, respectively. SMC-co-culture increases CD34(+)CD31(+) cell mobility, adhesion to and transmigration across ECs. Sorted CD34(+)CD31(+) progenitors that adhered to ECs co-cultured with SMCs have the capacity to form capillary-like structures in Matrigel and chimeric blood vessels in vivo. Sorted transmigrated progenitors give rise to macrophages, with increased pro-angiogenic activity. These differentiations of CD34(+)CD31(+) progenitors into ECs and macrophages are mediated by beta(2)-integrin and Notch-1, respectively. beta(2)-integrin and Notch-1 are activated by their counterligands, intercellular adhesion molecule-1 (ICAM-1) and jagged-1, which are highly expressed in the neoendothelium and neointima in injured arteries. Intraarterial injection of beta(2)-integrin-activated CD34(+)CD31(+) progenitors into wire-injured mice arteries inhibits neointima formation. CONCLUSION: Our findings indicate that the peripheral vascular niches composed of ECs and SMCs may predispose hematopoietic CD34(+)CD31(+) progenitors to differentiate into ECs and macrophages through the activations of the ICAM-1/beta(2)-integrin and jagged-1/Notch-1 cascades, respectively.
    日期: 2012-11
    關聯: Cardiovascular Research. 2012 Nov;96(2):296-307.
    Link to: http://dx.doi.org/10.1093/cvr/cvs256
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-6363&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000310156200032
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84867738349
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