Atherosclerotic plaque is the fatty material that builds up on arterial walls, where it can lead to heart disease and stroke. Atherosclerosis is currently treated with dietary changes, angioplasty (which uses a balloon to move the plaque aside) or more invasive procedures. Using drugs to break up these fatty plaques would be an enticing alternative, but delivery poses a problem. How do we precisely target the therapeutic agent to the diseased areas, leaving healthy tissues unaffected?
Dr. Erkki Ruoslahti and colleagues at Sanford-Burnham and UC Santa Barbara may have found a solution. For many years, Dr. Ruoslahti has been using specially designed peptides (pieces of proteins) to target cancer and other diseases. In a paper published online on April 11 by the Proceedings of the National Academy of Sciences, the Ruoslahti lab reports the discovery of a new peptide that can guide drugs or imaging agents specifically to atherosclerotic plaques.
“There are significant similarities between cancer and atherosclerosis, for example, both have a strong inflammatory component,” says Dr. Ruoslahti. “Thus, many of the lessons learned from selective drug delivery into tumors are likely to be applicable to atherosclerosis, opening up new diagnostic and therapeutic possibilities.”
The peptide, called LyP-1, binds to the receptor p32, which is often elevated in human cancers. Dr. Ruoslahti’s success using LyP-1 to target macrophages and lymphatic vessels in tumors, led him to believe that LyP-1 might also seek out atheroma-associated macrophages, which also express p32. The study found that LyP-1 does home to plaques and even penetrates them, leaving healthy tissues alone, a significant finding since previous homing peptides had generally only bound to the plaque surface.
The laboratory then collaborated with investigators at UC Davis in combining LyP-1 with MRI and PET scan contrast agents contained in nanoparticles. These also penetrated the plaque and led to successful scans of atherosclerotic mice. This technology could be used to carry small molecules and other therapeutics to diseased tissue.
Hamzah J, Kotamraju VR, Seo JW, Agemy L, Fogal V, Mahakian LM, Peters D, Roth L, Gagnon MK, Ferrara KW, & Ruoslahti E (2011). Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice. Proceedings of the National Academy of Sciences of the United States of America PMID: 21482787