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See detailEpigenetic modulators mitigate angiogenesis through a complex transcriptomic network
Shiva Shankar, T.V.; Willems, Luc ULg

in Vascular Pharmacology (2014), 60

In this review, we summarize the knowledge pertaining to the role of epigenetics in the regulation of angiogenesis. In particular, we show that lysine acetylation and cytosine methylation are important ... [more ▼]

In this review, we summarize the knowledge pertaining to the role of epigenetics in the regulation of angiogenesis. In particular, we show that lysine acetylation and cytosine methylation are important transcriptional regulators of angiogenic genes in endothelial cells. Lysine acetylation and cytosine methylation inhibitors idiosyncratically tune the transcriptome and affect expression of key modulators of angiogenesis such as VEGF and eNOS. Transcriptomic profiling also reveals a series of novel genes that are concomitantly affected by epigenetic modulators. The reversibility and overall tolerability of currently available epigenetic inhibitors open up the prospect of therapeutic intervention in pathologies where angiogenesis is exacerbated. This type of multitargeted strategy has the major advantage of overcoming the compensatory feedback mechanisms that characterize single anti-angiogenic factors. [less ▲]

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See detailNitric oxide-related products and myeloperoxidase in bronchoalveolar lavage fluids from patients with ALI activate NF-kappa B in alveolar cells and monocytes.
Nys, Monique ULg; Preiser, Jean-Charles ULg; Deby, Ginette ULg et al

in Vascular Pharmacology (2005), 43(6), 425-33

An increased production of NO* and peroxynitrite in lungs has been suspected during acute lung injury (ALI) in humans, and recent studies provided evidence for an alveolar production of nitrated compounds ... [more ▼]

An increased production of NO* and peroxynitrite in lungs has been suspected during acute lung injury (ALI) in humans, and recent studies provided evidence for an alveolar production of nitrated compounds. We observed increased concentrations of nitrites/nitrates, nitrated proteins and markers of neutrophil degranulation (myeloperoxidase, elastase and lactoferrine) in the fluids recovered from bronchoalveolar lavage fluids (BALF) of patients with ALI and correlated these changes to the number of neutrophils and the severity of the ALI. We also observed that BALFs stimulated the DNA-binding activity of the nuclear transcription factor kappa B (NF-kappaB) as detected by electrophoretic mobility shift assay in human alveolar cells (A549) and monocytes (THP1). The level of activation of the NF-kappaB-binding activity was correlated to the concentration of nitrated proteins and myeloperoxidase. Furthermore, in vitro studies confirmed that NO*-derived species (peroxynitrite and nitrites) and the neutrophil enzyme myeloperoxidase by themselves increased the activation of NF-kappaB, thereby arguing for an in vivo pathogenetic role of NO*-related products and neutrophil enzymes to human ALI. [less ▲]

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