Data from: Mechanism of anti-remodelling action of treprostinil in human pulmonary arterial smooth muscle cells

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 regard 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.