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Title: Applying side effects of anti fibrotic compounds to promote neovascularization for tissue engineering
Keywords: neovascularization, prolyl hydroxylase inhibitors, hypoxia inducible factor-1
Issue Date: 16-Apr-2008
Citation: WONG YUAN SY (2008-04-16). Applying side effects of anti fibrotic compounds to promote neovascularization for tissue engineering. ScholarBank@NUS Repository.
Abstract: Neovascularization and fibrosis represents two challenges in regenerative medicine and tissue engineering. One strategy to promote neovascularization is by targeting hypoxia inducible factor-1a (HIF-1a). This transcription factor is stabilized during hypoxia and in turn activates various proangiogenic genes including VEGF. The angiogenic and antifibrotic properties of hydralazine hydrochloride (HDZ), 2,4-pyridine dicarboxylic acid (PDCA) and ciclopirox olamine (CPX) was investigated because of their potential to cross-inhibit collagen- and HIF-prolyl hydroxylase. These substances induced angiogenesis in vitro by forming capillary like structures in co-cultures grown on tissue culture plates and in PLLA scaffolds; and in vivo, by inducing development of ectopic subintestinal vessels in zebrafish embryos. HIF-1a was stabilized in cell nuclei of fibroblast cultures and VEGF secretion was similarly increased. All substances showed antifibrotic effects, demonstrated by reduced collagen secretion in fibroblast cultures and decreased collagen content in zebrafish embryos.
Appears in Collections:Ph.D Theses (Open)

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