Mechanism of anti-remodelling action of treprostinil in human pulmonary arterial smooth muscle cells
| العنوان: | Mechanism of anti-remodelling action of treprostinil in human pulmonary arterial smooth muscle cells |
|---|---|
| المؤلفون: | Panja M. Boehm, Christoph Kornauth, Felicitas Oberndorfer, Walter Klepetko, Christopher Lambers, Michael Tamm, Michael Roth |
| المصدر: | PLoS ONE PLoS ONE, Vol 13, Iss 11, p e0205195 (2018) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, Cell signaling, Physiology, Cell, Becaplermin, lcsh:Medicine, Prostacyclin, 030204 cardiovascular system & hematology, Pharmacology, Signal transduction, Biochemistry, Extracellular matrix, 0302 clinical medicine, Endocrinology, Cyclic AMP, Medicine and Health Sciences, Myocyte, Familial Primary Pulmonary Hypertension, Lipid Hormones, Pulmonary Arteries, lcsh:Science, Mitogen-Activated Protein Kinase 1, Multidisciplinary, biology, Chemistry, Signaling cascades, Arteries, Middle Aged, Extracellular Matrix, medicine.anatomical_structure, Female, Cellular Structures and Organelles, Anatomy, medicine.drug, Research Article, Adult, Collagen Type IV, Myocytes, Smooth Muscle, Pulmonary Artery, Vascular Remodeling, Collagen Type I, Transforming Growth Factor beta1, 03 medical and health sciences, Growth Factors, medicine, Humans, Secretion, Cell Proliferation, Endocrine Physiology, lcsh:R, Connective Tissue Growth Factor, Biology and Life Sciences, Proteins, Cell Biology, Epoprostenol, Hormones, Extracellular Matrix Composition, Fibronectins, CTGF, Fibronectin, 030228 respiratory system, Gene Expression Regulation, TGF-beta signaling cascade, biology.protein, CCAAT-Enhancer-Binding Proteins, Cardiovascular Anatomy, Blood Vessels, lcsh:Q, Physiological Processes, Collagens, Treprostinil |
| الوصف: | Treprostinil is applied for pulmonary arterial hypertension (PAH) therapy. However, the mechanism by which the drug achieves its beneficial effects in PAH vessels is not fully understood. This study investigated the effects of treprostinil on PDGF-BB induced remodelling parameters in isolated human pulmonary arterial smooth muscle cells (PASMC) of four PAH patients. The production of TGF-β1, CTGF, collagen type-I and -IV, and of fibronectin were determined by ELISA and PCR. The role of cAMP was determined by ELISA and di-deoxyadenosine treatment. Proliferation was determined by direct cell count. Treprostinil increased cAMP levels dose and time dependently, which was not affected by PDGF-BB. Treprostinil significantly reduced PDGF-BB induced secretion of TGF-β1 and CTGF, both was counteracted when cAMP generation was blocked. Similarly, the PDGF-BB induced proliferation of PASMC was dose dependently reduced by treprostinil through signalling via cAMP-C/EBP-α p42 -p21(WAf1/Cip1). In regards to extracellular matrix remodelling, treprostinil significantly reduced PDGF-BB-TGF-β1-CTGF induced synthesis and deposition of collagen type I and fibronectin, in a cAMP sensitive manner. In contrast, the deposition of collagen IV was not affected. The data suggest that this action of treprostinil in vessel wall remodelling may benefit patients with PAH and may reduce arterial wall remodelling. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4115f92933d2ee65ee174483bcd59e5Test https://pubmed.ncbi.nlm.nih.gov/30383775Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d4115f92933d2ee65ee174483bcd59e5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|