ERA

Cardiovascular Research Centre (CVRC)

Through the assembly of an expert team, the CVRC aims to lessen the burden of cardiovascular diseases on society through the generation of new knowledge as to the underlying causes of these disorders.
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  1. Angiostatin inhibits endothelial MMP-2 and MMP-14 expression: A hypoxia specific mechanism of action [Download]

    Title: Angiostatin inhibits endothelial MMP-2 and MMP-14 expression: A hypoxia specific mechanism of action
    Creator: Radziwon-Balicka, A.
    Description: Angiostatin is an angiogenesis inhibitor in part generated by and released from platelets. Since platelets upon thrombus formation can give rise to areas of hypoxia, we investigated the effects of angiostatin on endothelial cell migration and apoptosis during hypoxia. Human microvascular endothelial cells (HMVEC-L) were exposed to angiostatin under normoxic or hypoxic conditions. Apoptosis was measured by flowcytometry. HMVEC-L migration was studied using a modified Boyden Chamber assay, in which migration is MMP-dependent. MMP-2, MMP-14, and VEGF levels were measured using immunoblot, Q-PCR and ELISA. During hypoxia HMVEC-L were protected from angiostatin-induced apoptosis due to increased hypoxia-induced VEGF expression. However, MMP-dependent migration of HMVEC-L was inhibited by angiostatin under hypoxic but not normoxic conditions. Angiostatin decreased MMP-2 at the gene and protein levels only in HMVEC-L exposed to hypoxia. A similar result was obtained for MMP-14. Higher angiostatin concentrations, as would be seen during thrombosis, induced HMVEC-L apoptosis, which was not rescued by VEGF. Under hypoxic conditions angiostatin’s primary anti-angiogenic mechanism is likely inhibition of endothelial cell MMP-dependent endothelial cell migration. Only at higher concentrations does angiostatin induce endothelial cell death. This study identifies a novel angiostatin anti-angiogenesis mechanism that is only triggered under pathological-like conditions.
    Subjects: Hypoxia, Matrix metalloproteinases, Angiostatin, Endothelial cells, Platelets
    Date Created: 2013
  2. Platelet-associated angiogenesis regulating factors: a pharmacological perspective [Download]

    Title: Platelet-associated angiogenesis regulating factors: a pharmacological perspective
    Creator: Radziwon-Balicka, A.
    Description: Platelets, in addition to maintaining hemostasis, also stimulate angiogenesis by generating and releasing, upon activation, factors that promote the growth of new blood vessels. To date, at least 20 angiogenesis-regulating factors have been identified in platelets, including both promoters and inhibitors. Platelet-derived angiogenesis regulators promote angiogenesis during wound healing, tumor growth, and in response to ischemia. Within platelets, angiogenesis regulators are primarily stored in alpha-granules, but are also found in the cytosol or derived from membrane lipids. Their release can be inhibited pharmacologically by anti-platelet agents, which consequently suppress platelet-stimulated angiogenesis. Several years ago, our research group discovered that platelets generate the angiogenesis inhibitor angiostatin independent of the activation state of platelets, and that platelet-derived angiostatin serves to limit the angiogenesis-stimulating effects of platelets. In this review, we summarize the current knowledge of platelet-associated angiogenesis regulators, how they impact angiogenesis, and how they are controlled pharmacologically.
    Subjects: Vascular endothelial growth factor, Hemostasis, Angiostatin, Angiogenesis regulators, Platelets, Alpha-granules, Angiogenesis, Endothlial cells, Thrombosis
    Date Created: 2012