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.

CVON Heart-Brain Connection Call open – deadline 23 Dec 2015

The CVON HBC Out of the Box call is open for applications from young, talented researchers (max. age 35 years at deadline for submission)

    • The subject should be within or complementary to the HBC consortium. See for the HBC programme details.
    • An overview of all criteria can be found in the proposal template.
    • Deadline for submission Wednesday December 23, 2015, 23.59h.


HBC Out of the Box proposal template

12-16 October – PhD training courses at Papendal

The PhD training courses bring young scientists in close contact with the latest scientific developments in the cardiovascular field. The courses are being held between October 12 – October 16, 2015 at Papendal. Register now. More information.

2015 Summer School Phaedra 30 sept – 2 okt

The Summer School will be organised by Daphne Merkus. Further details will be available soon.

Sharing the scientific knowledge and getting to know your (new) colleagues are the goals for the summer school.