Inhibition of PBEF is a possible therapeutic target for pulmonary hypertension

May 22, 2012

Inhibition of pre-B Cell Colony-Enhancing Factor (PBEF) could be a potential therapeutic target for pulmonary hypertension (PH), according to a preclinical study in an animal model of PH.

"PBEF expression appears to be significantly increased in PH. Accordingly, we examined whether inhibiting PBEF could prevent and reverse PH in rats," said Roberto Machado, MD, associate professor of medicine at the University of Illinois at Chicago. "We found that PBEF not only prevented the development of PH, but was able to reverse established PH, suggesting its potential use as a therapy for PH in humans."

The results will be presented at the ATS 2012 International Conference in San Francisco.

In the study, rats were given one dose of monocrotaline to induce PH.Two sets of experiments were performed: prevention experiments,in which inhibition of PBEF was performed simultaneously with administration of monocrotaline, and reversal experiments, in which PBEF inhibition was performed two weeks after administration of monocrotaline when PH was already established in the animals.

In the prevention experiments, inhibition of PBEF prevented the development of PH and right ventricular hypertrophy. In the reversal experiments, inhibition of PBEF reversed established PH. In additional experiments in a cell culture model using human pulmonary arterial , treatment with recombinant PBEF enhanced store-operated calcium entry, which is involved in sustained pulmonary vasoconstriction and , suggesting a possible mechanism for the observed effects of PBEF inhibition in PH.

"If the prevention and reversal of PH with PPEF inhibition that we observed in our preclinical model can be replicated in humans, it might offer a new approach to the treatment of patients with PH," said Dr. Machado. "Further studies are needed to confirm and expand upon our early results."

Explore further: Ganetespib showed activity in KRAS-mutant NSCLC as monotherapy and in combinations

More information: "Inhibition Of Pre-B Cell Colony-Enhancing Factor (PBEF) Prevents And Reverses Monocrotaline-Induced Pulmonary Hypertension" (Session C17, Tuesday, May 22, 2012: Room 2001-2003, Moscone Center; Abstract 29757)

Related Stories

Recommended for you

Zika virus infection alters human and viral RNA

October 20, 2016

Researchers at University of California San Diego School of Medicine have discovered that Zika virus infection leads to modifications of both viral and human genetic material. These modifications—chemical tags known as ...

Food-poisoning bacteria may be behind Crohn's disease

October 19, 2016

People who retain a particular bacterium in their gut after a bout of food poisoning may be at an increased risk of developing Crohn's disease later in life, according to a new study led by researchers at McMaster University.

Neurodevelopmental model of Zika may provide rapid answers

October 19, 2016

A newly published study from researchers working in collaboration with the Regenerative Bioscience Center at the University of Georgia demonstrates fetal death and brain damage in early chick embryos similar to microcephaly—a ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.