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

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

January 11, 2012
The investigational drug ganetespib, a synthetic second-generation Hsp90 inhibitor, slowed the growth of cancer cells taken from non-small cell lung cancer tumors with a mutation in the KRAS gene. The drug was even more active ...

Combination therapy shows potent tumor growth inhibition in preclinical studies

November 13, 2011
Combining the investigational agents REGN910 and aflibercept yielded statistically significant improvements in antitumor effects in animal models compared with either agent alone, according to results presented at the AACR-NCI-EORTC ...

Recommended for you

Groundbreaking investigative effort identifies gonorrhea vaccine candidates

September 19, 2017
Researchers at Oregon State University have identified a pair of proteins that show promise as the basis for a gonorrhea vaccine.

Snail fever progression linked to nitric oxide production

September 14, 2017
Bilharzia, caused by a parasitic worm found in freshwater called Schistosoma, infects around 200 million people globally and its advance can lead to death, especially in children in developing countries.

Systems analysis points to links between Toxoplasma infection and common brain diseases

September 13, 2017
More than 2 billion people - nearly one out of every three humans on earth, including about 60 million people in the United States - have a lifelong infection with the brain-dwelling parasite Toxoplasma gondii.

Study clears important hurdle toward developing an HIV vaccine

September 13, 2017
An international team of researchers has demonstrated a way of overcoming one of the major stumbling blocks that has prevented the development of a vaccine against HIV: the ability to generate immune cells that stay in circulation ...

As 'flesh-eating' Leishmania come closer, a vaccine against them does, too

September 13, 2017
Parasites that ulcerate the skin, can disfigure the face, and may fatally mutilate its victim's internal organs are creeping closer to the southern edges of the United States.

Promising clinical trial results could give doctors a new tool against drug-resistant strains of malaria parasite

September 13, 2017
Tulane University researchers have developed a new drug that is effective against non-severe cases of malaria, according to results from an FDA-supervised clinical trial published in the latest issue of The Lancet Infectious ...

0 comments

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.