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A high pressure in the pulmonary circulation (pulmonary hypertension, PH) complicates several highly prevalent chronic diseases, including left heart failure and chronic thrombo-embolic disease. Pulmonary arterial hypertension (PAH) is a fatally progressive form of PH with characteristic changes in small lung arteries, affecting 1/50.000 humans. Regardless of primary cause, PH almost invariably leads to right heart failure and death.
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Premature aging of the lung vasculature explains the progression of pulmonary arterial hypertension, and this ‘irreversible’ process can be reversed by a new anti-aging drug

Researchers from the PHAEDRA-consortium have identified a new essential mechanism that causes the irreversible occlusion of lung vessels in patients with pulmonary arterial hypertension (PAH), and found a drug able to reverse this ‘irreversible’ process. These promising findings were published today in Science Translational Medicine.

In patients with PAH, vessels in the lung progressively occlude and cause high pulmonary blood pressure. PAH is a fatal condition that can already present in childhood, for example in children born with a heart defect. Luckily, early diagnosis and correction of the heart defect can completely reverse PAH. But if the surgery is performed too late, the disease has lost its reversibility, the high pulmonary blood pressure will increase and cause heart failure at a young age.

“It has been known since the 1950’s that PAH has this reversible and an irreversible stage…” states first author dr. van der Feen, “…but thus far, we still don’t understand why this disease becomes irreversible”. Senior author professor Rabinovitch, Stanford University notes: “The mechanism behind this reversibility has been one of the big questions in the field, and this study provides an important clue.”            

The team of the University of Groningen, the Netherlands, led by pediatric cardiologists professor Berger and dr. Bartelds mimicked a congenital heart defect in rats, and found that PAH developed in a pattern similar to humans, with a reversible and an irreversible stage. The researchers then compared the genetic profile of these rats using bioinformatic techniques at Stanford University, USA, and found that these profiles are essentially different. Under the microscope, the irreversible vessels had increased numbers of so called ‘senescent’ cells: cells that have aged prematurely and have lost their normal function. These cells typically cannot be cleared by the body, because they have become resistent to normal programmed cell death. Accumulation of senescent cells causes the surrounding tissue to degenerate, due to the continuous release of inflammatory factors.

It is for the first time that the presence of these senescent cells has been directly associated with irreversible PAH. So, could clearance of senescent cells also help to reverse ‘irreversible’ PAH? In collaboration with the European Institute for the Biology of Aging, the research group together with scientists form the LUMC and VUMC showed that the experimental ‘anti-aging drug’ ABT-263 is able to selectively kill the senescent cells in the lung vessels, while the healthy ones remain unaffected. ABT-263 was finally administered to rats with irreversible PAH and showed to reverse vessel occlusion and reduce the high blood pressure in the lungs. Moreover, the drug also seemed to stimulate vessel regeneration in the diseased lungs.

Dr. Van der Feen concludes:  “These findings may explain why PAH progresses and offers a new line of treatment that has the potential to reverse this disease, that has appeared so ‘irreversible’ thus far.” Currently, no treatments with curative potential exist for patients with PAH.


Dutch CardioVascular Alliance (DCVA) Leadership Programme

Dutch CardioVascular Alliance (DCVA) Leadership Programme – deadline Oct 31st, 2019

Met dit bericht informeren we je graag over het DCVA Leadership Program en de mogelijkheid voor talenten om zich hiervoor aan te melden.
De Dutch CardioVascular Alliance (DCVA) heeft dit programma opgezet om talentvolle experts in het cardiovasculaire veld (o.a. wetenschappers, ervaringsexperts, zorgprofessionals en technici) de mogelijkheid te bieden hun leiderschapskwaliteiten verder te ontwikkelen.
Dit zullen zij doen door in multidisciplinaire teams van drie à vier personen te werken aan verschillende actuele vraagstukken in het cardiovasculaire veld, ingebracht door DCVA partners.
Het tweejarige programma zal een netwerk vormen van cardiovasculaire talenten met verschillende achtergronden en hen klaarstomen als leiders in het cardiovasculaire veld van de toekomst.
Hier vind je de brochure met informatie over de opzet en het doel van het programma, begeleiding, aanmeldingsprocedure, en onderwerpen van de vraagstukken.

Geïnteresseerden kunnen zich tot 31 oktober aanmelden door een mail te sturen naar talent@dcvalliance.nl met de volgende documenten;
– een steunbrief van de huidige leidinggevende voor deelname aan het programma.

Begin november horen de geïnteresseerden of ze worden uitgenodigd voor een persoonlijke pitch eind november waarna ze geïnformeerd zullen worden over deelname aan het programma.

Heb je vragen over het programma? Neem gerust contact op met de organisatie via talent@dcvalliance.nl