[Update in basic research in the therapy of pulmonary arterial hypertension].
Pulmonary hypertension is a vasculoproliferative disorder which is characterized by vasoconstriction and proliferation of vascular cells within the vessel wall. Mostly addressing the increased vascular tone, prostacyclin and its analogues, endothelin-receptor antagonists and phosphodiesterase type 5 inhibitors have been approved for treatment of PAH and represent the current therapeutic options. Currently, research focuses on the development of causal treatment regimens aiming a normalization of the vessel structure. Mechanistically, increased proliferation, migration and a resistance to apoptosis of vascular cells represent key events in disease progression. In clinical relevant animal models of pulmonary hypertension, new non-vasoactive drugs could not only attenuate ("Anti-Remodeling") but reverse ("Reverse-Remodeling") the disease. These compound classes include tyrosine kinase inhibitors, elastase inhibitors, and phosphodiesterase inhibitors. For some of these agents clinical trials are already initiated which will address safety and efficacy. In addition, there is further development of new vasodilators addressing well known and new signaling pathways. Taken together, there is advanced research in the field of pulmonary vascular diseases and the efficacy of several new drugs is currently addressed in clinical trials.
Schermuly
R
R
Max-Planck-Institut für Herz und Lungenforschung, Bad Nauheim. ralph.schermuly@mpi-bn.mpg.de
Grimminger
F
F
D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D011505:Protein-Tyrosine Kinases; D010196:Pancreatic Elastase