Pulmonary arteries carry blood from the heart to the lungs, where they pick up fresh oxygen for distribution to the rest of the body. Since almost every cell in the human body needs oxygen in order to convert nutrients into energy, pulmonary artery function is crucial. Pulmonary arterial hypertension (PAH) occurs when pressure builds up in these blood vessels, impairing this function. People with PAH experience shortness of breath, fatigue and chest pain. As the condition worsens, the heart has to work harder and harder to pump blood, sometimes leading to heart failure.
Despite eight approved clinical therapies for PAH and additional therapies currently in trials, there is no cure. What’s more, current treatments don’t specifically target pulmonary arteries, which can lead to severe side effects.
Sanford-Burnham scientists, led by Drs. Masanobu Komatsu and Dr. Takeo Urakami, in collaboration with VBS Pharmaceuticals, recently discovered a peptide (a short protein) that selectively targets and penetrates lung blood vessels affected by PAH. When the team tested this peptide, called CARSKNKDC (or CAR for short) in a rodent model of PAH, it homed in on hypertensive lungs, but spared healthy lungs and other organs. CAR also accumulated in other regions of the respiratory system that play crucial roles in PAH development and progression.
Published in the June 2011 issue of the American Journal of Pathology, these findings indicate that CAR could be used to deliver therapeutic compounds and imaging probes directly to PAH lungs.
“The use of peptides for human therapy is a growing concept within the pharmaceutical industry,” says senior author Dr. Komatsu in a statement released by VBS Pharmaceuticals. “The successful targeting of the pulmonary system utilizing the CAR peptide can offer unique opportunities to target multiple cell types important in the pathogenesis of PAH.”
This study was named “recommended reading” by the Faculty of 1000 (F1000), a prestigious group of scientists who were selected by their peers to represent their respective research fields. F1000 Faculty Members (now actually numbering more than 2,300 scientists) review, rank and recommend published papers to give other scientists the inside scoop on what they feel are the most important papers in a given field. Selection and evaluation of this paper places it in F1000’s library of the top two percent of published articles in biology and medicine.
Sanford-Burnham scientists are also developing targeted peptide technologies to improve drug delivery for other diseases. Read more on Beaker:
Targeting Arterial Plaque
New Insights into Scar Prevention
Targeting Prostate Tumors with Nanoworms
Making Cancer Treatments Better
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Original paper:
Urakami T, Järvinen TA, Toba M, Sawada J, Ambalavanan N, Mann D, McMurtry I, Oka M, Ruoslahti E, & Komatsu M (2011). Peptide-directed highly selective targeting of pulmonary arterial hypertension. The American journal of pathology, 178 (6), 2489-95 PMID: 21549345
