Category Archives: 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.

May 26th consortium meeting in Amsterdam

On Tuesday May 26th, the Q2-meeting will be held at the VUmc in Amsterdam. The meeting will start at 13:00 and end around 17:30  (Programme). The Scientific Advisory Board will be present and give two presentations for our researchers.

June 30th 2014 Consortium Meeting in Amsterdam VUMC

The consortium meeting for the second quarter 2014 will be held at the VUMC in Amsterdam. The meeting will start at 13:00 with lectures by Victor van Hinsberg and Nick Morrell followed at 16:00 by the presentations of the Phaedra members showing their progress in their work package.

February 7th 2014 Consortium Meeting in Groningen

The second consortium meeting of the Phaedra project has been held on the 7th of February at the UMC in Groningen. All partners gave a presentation on their progress in their work package and on their future plans to reach the milestones. Tieneke Schaaij-Visser from the Hartstichting was present and gave a nice overview on the work of the Hartstichting.

The meeting was continued with the “Cell Culture Meeting” where several protocols on cell culturing were discussed.

September 30th 2013 Kick-off Meeting Phaedra

The Phaedra consortium started 1st September 2013. The kick-off meeting was held on September 30th 2013 at the VUMC in Amsterdam. All partners were present and explained their plans on how to reach the deliverables and milestone within their Work Package.
Financial, organizational issues and planning were also discussed to ensure a well organised consortium.

cake The Phaedra project being granted by CVON was celebrated with a wonderful cake.