Zusammenfassung
Die pulmonale arterielle Hypertonie (PAH) wird derzeit mit Substanzen
behandelt, die primär eine Wiederherstellung der Balance
des pulmonalvaskulären Tonus bewirken – namentlich
die Prostanoide, Antagonisten des Endothelinrezeptors und die PDE-5-Inhibitoren – auch
wenn diese Substanzen auch antiproliferative Effekte besitzen. Andere
Substanzen, die direkt das Remodeling der Pulmonalarterien adressieren,
werden derzeit nicht nur in präklinischen Tiermodellen, sondern
auch bereits in klinischen Studien untersucht. Der Fokus der Grundlagenforschung liegt
dabei sowohl auf der Ebene von Mediatoren und Rezeptoren, auf der
Ebene von intrazellulären Signaltransduktionswegen und
Transkriptionsfaktoren, sowie auf der Ebene der Effektoren.
Summary
Pulmonary arterial hypertension is a life-threatening, vasculoproliferative
disease of the lung, which is characterized by vasoconstriction
and remodeling of small pulmonary arteries. Drugs for the treatment
of PAH mainly address the increased vascular tone. Substances like
prostacyclin, endothelin-receptor-antagonists and phosphodiesterase-5-inhibitors
have been approved for the treatment of PAH and represent the current
therapeutic options. The development of a causal treatment aiming
a normalization of the vessel wall structure is the current focus
of research. The key events in disease progression are represented
by increased proliferation, migration and a resistance to apoptosis
of pulmonary vascular cells. Therefore, new non-vasoactive drugs
are investigated in relevant preclinical animal models of pulmonary
arterial hypertension. Some of these substances, like tyrosine kinase inhibitors,
elastase inhibitors and phosphodiesterase-1-inhibitors, could not
only attenuate (anti-remodeling) but reverse (reverse-remodeling) the
disease. Additionally, new vasodilators, like soluble guanylate
cyclase stimulators and activators, addressing well-known and new
signaling pathways are currently under investigation. Taken together,
with increasing insight into the pathology of PAH, several novel
drug targets and treatments have emerged which may improve the management
of patients and which efficacy is currently addressed in preclinical
studies and clinical trials.
Schlüsselwörter
pulmonale arterielle Hypertonie - Gefäßremodeling - Vasokonstriktion
Keywords
pulmonary arterial hypertension - vascular remodeling - vasoconstriction
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Prof. Dr. Ralph Schermuly
Max-Planck-Institut für Herz- und
Lungenforschung
Parkstraße 1
61231
Bad Nauheim
Telefon: 06032/705380
eMail: ralph.schermuly@mpi-bn.mpg.de