CD105 (endoglin), apoptosis, and stroke.
نویسندگان
چکیده
welcomes Letters to the Editor and will publish them, if suitable, as space permits. They should not exceed 750 words (excluding references) and may be subject to editing or abridgment. Please submit letters in duplicate, typed double-spaced. Include a fax number for the corresponding author and a completed copyright transfer agreement form (published in every issue). To the Editor: The recent paper by Zhu et al 1 in this journal provides an insight into the possible mechanism of hypoxia-induced upregu-lation of CD105 (endoglin). The following 3 points are relevant to their paper. Lately there has been a major debate regarding the relevance of cell culture/animal models for human stroke in general and for angiogenesis in particular. Some authors maintain that the failure of current therapies for stroke in humans based on the use of animal models is possibly owing to the fact that the pathobiology of human stroke is not mirrored by experimentally-induced stroke in animal models. If true, it would limit the value findings of Zhu et al, 1 which are based on the use of murine endothelial cell culture and an in vivo mouse model of focal cerebral ischemia. However, there is strong evidence to discount this possibility. First, CD105 has been found to be highly expressed in the penumbra region of human stroke. 2 Second, soluble CD105 levels in plasma have been found to be high in patients with stroke (our unpublished data, 2004). Furthermore, human vascular, like murine, endothelial cells showed an upregulation of CD105 expression when cultured under hypoxic conditions, although there were some notable differences in the 2 studies. 1,3 Hypoxia and Apoptosis Li et al 3 reported that hypoxia-induced upregulation of CD105 prevented vascular endothelial cells from undergoing TGF-– induced cell apoptosis. The overexpression of CD105 in hypoxic cells ameliorated cell apoptosis either with or without TGF-1, the conclusion being that CD105 functions via TGF-1 signaling plus another independent pathway, as yet unknown. Since only 1% of CD105 binds to TGF-, the function of the remaining 99% remains unknown. 4 Protection against apoptosis by CD105 could be one of its new functions. Schematic model illustrates the possible role of CD105 in hypoxia mediated angiogenesis. Hypoxia increases the expression and transcriptional activity of HIF-1a which enhances the expression of CD105 by binding with a hypoxia response element (HRE) in the CD105 promoter. Augmented CD105 indirectly through integrin or other adaptor proteins (?), phosphorylates and …
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ورودعنوان ژورنال:
- Stroke
دوره 35 5 شماره
صفحات -
تاریخ انتشار 2004