A crucial role of caldesmon in vascular development in vivo.
ABSTRACT We explored the in vivo effects of knockdown of caldesmon on vascular development in zebrafish.
We investigated the effects of caldesmon knockdown on the vascular development in a zebrafish model with special attention for the trunk and head vessels including the aortic arches. We examined the developing fishes at various time points. The vascular abnormalities observed in the caldesmon morphants were morphologically and functionally characterized in detail in fixed and living embryos. The knockdown of caldesmon caused serious defects in vasculogenesis and angiogenesis in zebrafish morphants, and the vascular integrity and blood circulation were concomitantly impaired.
The data provide the first functional assessment of the role of caldesmon in vascular development in vivo, indicating that this molecule plays a crucial role in vasculogenesis and angiogenesis in vivo. Interfering with caldesmon opens new therapeutic avenues for anti-angiogenesis in cancer and ischaemic cardiovascular disease.
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ABSTRACT: There are various zebrafish models with cardiovascular defects which adequately mimic the impaired circulation and tissue perfusion of various human cardiovascular diseases. Zebrafish embryos/larvae are optically transparent, and the systemic blood circulation can be recorded by using a microscope with video imaging. We detected a series of circulatory defects in our caldesmon and glucose transport 1 knockdown zebrafish models, including arteriovenous (AV) shunting, collateral circulation, AV fusion, vessel bifurcation, reduced or depleted regional perfusion, sinus venous (SV) rupture, and more. The quick detection by simple video imaging of various pathological states of the blood circulation in the living zebrafish embryos/larvae is non-invasive and cost-effective. The method is suitable for large scale screening of altered blood circulation in various zebrafish models with impaired cardiovascular development. This is a powerful approach of live digital data communication in biomedical research and teaching.08/2013; DOI:10.2991/icaicte.2013.173
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ABSTRACT: Glioblastoma (GB) displays diffusely infiltrative growth patterns. Dispersive cells escape surgical resection and contribute to tumor recurrence within a few centimeters of the resection cavity in 90% of cases. We know that the non-neoplastic stromal compartment, in addition to infiltrative tumor cells, plays an active role in tumor recurrence. We isolated a new stromal cell population from the histologically normal surgical margins of GB by computer-guided stereotaxic biopsies and primary culture. These GB-associated stromal cells (GASCs) share phenotypic and functional properties with the cancer-associated fibroblasts (CAFs) described in the stroma of carcinomas. In particular, GASCs have tumor-promoting effects on glioma cells in vitro and in vivo. Here, we describe a quantitative proteomic analysis using iTRAQ labeling and mass spectrometry to compare GASCs with control stromal cells derived from non-GB peripheral brain tissues. A total of 1077 proteins were quantified and 67 proteins were found to differ between GASCs and control stromal cells. Several proteins changed in GASCs are related to a highly motile myofibroblast phenotype, and to wound healing and angiogenesis. The results for several selected proteins were validated by western blotting or flow cytometry. Furthermore, the effect of GASCs on angiogenesis was confirmed with the orthotopic U87MG glioma model. In conclusion, GASCs, isolated from GB histologically normal surgical margins and found mostly near blood vessels are a vascular niche constituent establishing a permissive environment facilitating angiogenesis and possibly colonization of recurrence-initiating cells. We identify various proteins as being expressed in GASCs: some of these proteins may serve as prognostic factors for GB and/or targets for anti-glioma treatment.The Journal of Pathology 01/2014; 233(1). DOI:10.1002/path.4332 · 7.33 Impact Factor
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ABSTRACT: The blood-brain barrier (BBB) is a complex feature of brain endothelial cells that restricts the passage of blood-borne molecules into the brain parenchyma, while ensuring the delivery of essential nutrients and selected biomolecules. Brain vasculature is anatomically distinct from that of other organs and comprises in addition to endothelial cells, pericytes and astrocytes, which collectively form the neurovascular unit (NVU). This review focuses on the regulation of BBB properties by the NVU and the periphery. A brief overview of cellular components of the NVU, and BBB characteristics will be provided, with more emphasis placed on the molecular mechanisms involved in the development of brain vasculature and human genetic diseases primarily affected by dysfunction of components of the NVU. In addition, the regulation of brain vasculature by peripheral factors such as diet and systemic disease is discussed.Schweizerische medizinische Wochenschrift 11/2013; 143:w13892. DOI:10.4414/smw.2013.13892 · 1.88 Impact Factor