HYDROGEN SULFIDE A NEW ENDOGENOUS REGULATOR OF ANGIOGENESIS: SINGALLING, PHYSIOLOGY/PATHOPHYSIOLOGY AND DEVELOPMENT OF PHARMACOLOGICAL INHIBITORS

Abstract: 

Hydrogen sulfide (H2S) is generated in mammalians from L-cysteine in a cell type- and tissue-specific manner, by cystathione-?²-synthase and cystathionine-?³-lyase. H2S participates in the regulation of nervous and cardiovascular system functions, cellular metabolism, and immune/inflammatory responses. In spite of recent advances in H2S biology, the molecular mechanisms through which H2S affects cell functions remain unexplored.

The aims of the proposed study are to:

  1. elucidate the molecular mechanisms of action of H2S in vascular endothelial and smooth muscle cells,
  2. analyze the contribution of H2S in disease processes and correlate H2S function with angiogenesis in diseased tissues, and
  3. generate novel pharmacological inhibitors of H2S production.

Our proposal is composed of 7 workpakages (WPs).

  1. WP1 concern the coordination of the project that involves 11 principle investigators from 5 universities and 2 research institutes.
  2. In WP2 we will investigate H2S signaling and correlate the molecular events with key endothelial and smooth muscle functions (cell survival, angiogenesis, permeability, relaxation).
  3. In WP3 will evaluate the role of endogenous H2S in the development of the vascular system using genetics-based approaches in zebrafish, and analyze H2S-dependent transcriptome changes during development of the vascular system using microarrays.
  4. WP4 will focus on the role of H2S in vascular permeability.
  5. In WP5 we will study the production of H2S during pathophysiological conditions and link it to changes in angiogenesis in 2 model systems. The role of H2S will be evaluated in angiogenesis and disease progression in experimental colitis; the role of H2S in pathological angiogenesis and altered contractility of the diaphragm will be tested during resistive breathing.
  6. In WP6 we will design, synthesize and evaluate novel H2S production inhibitors.
  7. WP7 consists of all the dissemination activities related to results obtained from our proposed studies.

Project info

Acronym:
H2SBIOLOGY
Coordinating Institution:
University of Patras
Scientific Coordinator:
Papapetropoulos Andreas
Research Team 2 Leader:
Karalis Katia
Research Team 3 Leader:
Vourloumis Dionysis

Stats

I.D.:
565
Mis:
380259
Duration (months):
44
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β41Ω9-25Ρ

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