Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Kiss, T; Kovacs, K; Komocsi, A; Tornyos, A; Zalan, P; Sumegi, B; Gallyas, F; Kovacs, K.
Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.
PLoS One. 2014; 9(8): e104890
Doi: 10.1371/journal.pone.0104890
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Tornyos Adrienn
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Pulmonary arterial hypertension (PH) is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT)-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK) phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt) pathway and nuclear factor (NF)-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP)-1, interleukin (IL)-1α, lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.
- Find related publications in this database (using NLM MeSH Indexing)
- Active Transport, Cell Nucleus - drug effects
- Animals - administration & dosage
- Cell Nucleus - metabolism
- Chemokines - metabolism
- Enzyme Activation - administration & dosage
- Hypertension, Pulmonary - drug therapy, metabolism
- Lung - drug effects, metabolism
- MAP Kinase Signaling System - drug effects
- Mitogen-Activated Protein Kinases - metabolism
- NF-kappa B - metabolism
- Piperazines - pharmacology, therapeutic use
- Proto-Oncogene Proteins c-akt - metabolism
- Purines - pharmacology, therapeutic use
- Rats - administration & dosage
- Sildenafil Citrate - administration & dosage
- Sulfonamides - pharmacology, therapeutic use
- Vasodilator Agents - pharmacology, therapeutic use