Wiebke Janssen

Publications of Wiebke Janssen

• Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension.

  Authors: Djuro Kosanovic, Baktybek Kojonazarov, Himal Luitel, Bhola K Dahal, Akylbek Sydykov, Teodora Cornitescu, Wiebke Janssen, Ralf P Brandes, Neil Davie, Hossein A Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Ralph T Schermuly

  Respiratory research. 06/2011; 12:87.

  Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure theEndothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension.

• Riociguat for the treatment of pulmonary hypertension.

  Authors: Ralph T Schermuly, Wiebke Janssen, Norbert Weissmann, Johannes-Peter Stasch, Friedrich Grimminger, Hossein Ardeschir Ghofrani

  Expert opinion on investigational drugs. 03/2011; 20(4):567-76.

  INTRODUCTION: Pulmonary hypertension (PH) is a severe condition with a poor prognosis despite recent treatment advances. Therapies with new mechanisms of action are needed. AREAS COVERED: This reviewINTRODUCTION: Pulmonary hypertension (PH) is a severe condition with a poor prognosis despite recent treatment advances. Therapies with new mechanisms of action are needed. AREAS COVERED: This review will help readers understand the mechanism of action of the soluble guanylate cyclase (sGC) stimulator riociguat (BAY 63-2521) and will provide a comprehensive summary regarding efficacy and safety of this drug in the management of PH. The most relevant publications up to December 2010 were used as sources for this review. EXPERT OPINION: Cyclic guanosine monophosphate (cGMP) is an important mediator of the preferential perfusion of well-ventilated regions throughout the lung. Drugs that increase cGMP levels could promote pulmonary vasorelaxation while maintaining optimal gas exchange. cGMP is generated by sGC, which can be stimulated by nitric oxide (NO). Riociguat stimulates sGC independently of NO and increases the sensitivity of sGC to NO, resulting in increased cGMP levels. Results to date suggest rapid, potent and prolonged efficacy and good tolerability in different types of PH. Phase III clinical trials are evaluating the long-term safety and clinical effectiveness of riociguat in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. Riociguat has the potential to become an important drug for the treatment of patients with PH.

• Impaired left-ventricular cardiac function in male GPR30-deficient mice.

  Authors: Martina Delbeck, Stefan Golz, Richardus Vonk, Wiebke Janssen, Tim Hucho, Jörg Isensee, Stefan Schäfer, Christiane Otto

  Molecular medicine reports. 01/2011; 4(1):37-40.

  G-protein-coupled receptor 30 (GPR30) has been reported to act as a membrane-bound estrogen receptor that is involved in the mediation of non-genomic estradiol signalling. In this study, weG-protein-coupled receptor 30 (GPR30) has been reported to act as a membrane-bound estrogen receptor that is involved in the mediation of non-genomic estradiol signalling. In this study, we demonstrated that male, but not female, GPR30-deficient mice suffer from impaired left‑ventricular cardiac function. Left ventricles from male mutant mice were enlarged. There were no malformations in the valves or outflow tract of the heart. Both the contractility and relaxation capacity of the left ventricle were reduced, leading to increased left‑ventricular end-diastolic pressure in GPR30-deficient mice. In conclusion, our data support a role for GPR30 in the gender-specific aspects of heart failure.

• Chronic inhibition of phosphodiesterase 5 does not prevent pressure overload induced right ventricular remodelling.

  Authors: Stefan Schäfer, Peter Ellinghaus, Wiebke Janssen, Frank Kramer, Klemens Lustig, Hendrik Milting, Raimund Kast, Martina Klein

  Cardiovascular research. 02/2009;

  AIMS: Inhibition of phosphodiesterase 5 (PDE5) decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension. It is unclear however, whether inhibition of PDE5AIMS: Inhibition of phosphodiesterase 5 (PDE5) decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension. It is unclear however, whether inhibition of PDE5 can prevent myocardial remodelling during right ventricular pressure overload. METHODS: Right ventricular pressure overload was produced in male rats in a pulmonary hypertension model (monocrotaline 60 mg/kg s.c.) or by surgical pulmonary artery banding. PDE5 inhibition using oral sildenafil (50 mg/kg/d in drinking water) or placebo was initiated 14 days after monocrotaline treatment and continued for 14 days until final examination. In the pulmonary artery banding groups, rats were treated with sildenafil (50 mg/kg/d) or placebo for 21 days following surgical pulmonary artery banding. At the final experiments, right ventricular haemodynamics were measured and remodelling was analyzed using histological, biochemical and gene expression markers. RESULTS: Both monocrotaline and pulmonary artery banding increased right ventricular systolic pressure to approximately 80 mmHg. In parallel, both interventions induced markers of hypertrophy (upregulation of natriuretic peptides, increase in myocyte diameter) and fibrosis (upregulation of collagen types 1A2 and 3A1) as well as mRNA expression of the tissue inhibitor of matrix metalloproteases 1 and osteopontin in the right ventricle. In monocrotaline model, sildenafil decreased pulmonary pressure, reduced right ventricular hypertrophy and prevented fibrosis marker gene upregulation. After pulmonary artery banding, in contrast, sildenafil increased markers of myocardial remodeling and right ventricular myocyte diameter. CONCLUSIONS: Sildenafil prevents myocardial remodelling in pulmonary hypertension through an indirect action via right ventricular unloading.