Molecular therapy for pulmonary arterial hypertension: Tadalafil [Brand name: Cialis, Adcirca and others], a cGMP-specific phosphodiestrase type 5 inhibitor used in the treatment of erectile dysfunction and pulmonary arterial hypertension, inhibits the development of pulmonary arterial hypertension via down regulation of its target gene Notch3, 20/January/2018, 11.33 pm

What they say: 

A study from the University of California, La Jolla, California, USA shows that “Notch3 signaling promotes the development of pulmonary arterial hypertension.” This study was published, in the 15 November  2009 issue of the journal “Nature Medicine”[the number 1 journal in General Medicine with an I.F of 28.054],  by Prof. Thistlethwaite PA, Li X and others.

What we say: 

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Molecular therapy for pulmonary arterial hypertension: Tadalafil [Brand name: Cialis, Adcirca and others], a cGMP-specific phosphodiestrase type 5 inhibitor used in the treatment of erectile dysfunction and pulmonary arterial hypertension, inhibits the development of pulmonary arterial hypertension via down regulation of its target gene Notch3

Significance of the study:  

Tadalafil has been shown to aid in the treatment of pulmonary arterial hypertension. However, its mechanism of action is far from understood. 

This study suggests, for the first time, that Tadalafil, by increasing the expression of its target gene, it may decrease, in dose-dependent manner, the expression of Notch3 and its target gene Hes-5 (Fig.1). Thereby, it may inhibit and promote, respectively, proliferation and differentiation of smooth muscle cells. And, thereby, prevent pulmonary hypertension (Figure 1).  Thus, pharmacological formulations encompassing “Tadalafil  or its analogues, either alone or in combination with other drugs,“ may be used to treat pulmonary arterial hypertension (Figure 2).

Figure 1. Mechanistic insights into how Tadalafil inhibits the development of pulmonary hypertension through regulation of its target genes

Figure 2. The chemical structure of Tadalafil

Details of the research findings: 

Idea Proposed/Formulated by: Dr L Boominathan Ph.D.

Undisclosed mechanistic information: How Tadalafil decreases the expression of Notch3 and its target gene

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References: 

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Citation: Boominathan, L.,  Molecular therapy for pulmonary arterial hypertension: Tadalafil [Brand name: Cialis, Adcirca and others], a cGMP-specific phosphodiestrase type 5 inhibitor used in the treatment of erectile dysfunction and pulmonary arterial hypertension, inhibits the development of pulmonary arterial hypertension via down regulation of its target gene Notch3, 20/January/2018, 11.33 pm,  Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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