In spite of numerous medical breakthroughs ranging from heart transplants to bypass surgery, cardiovascular disease still tops the list as the leading cause of death in developed countries. Key among the many problems that trouble our hearts is something called myocardial ischemia disease (MID), a condition that leads to reduced blood flow in the vessels of the heart and lower extremities and, frequently, corrective surgery. Now, University of Texas at Austin (UTA) biomedical engineer Aaron Baker and his research team have developed a method that may speed up the body's ability to grow new blood vessels (a phenomenon called angiogenesis), and best of all, no surgery is required. That's potentially great news for the nearly 27 million folks in the U.S. alone who chronically suffer from MID.

Previous work in triggering angiogenesis to reverse ischemia has centered around treating target tissues with a growth factor called FGF-2 (fibroblast growth factor 2), but getting it to bind to extracellular receptors has been difficult at best.

"Others have tried using growth factors to stimulate vessel growth in clinical trials and have not been successful," Baker said. "We think that a major reason for this is that previous methods assumed that the diseased tissues retained the ability to respond to a growth stimulus. Our method basically delivers extra components that can restore growth factor responsiveness to the tissue of patients with long-standing clinical disease."

To boost the growth factor's effectiveness, the researchers hit upon the novel approach of encasing it in lipid-based nanoparticles (proteoliposomes) that contain a cell division-promoting co-receptor called syndecan-4. When injected into rats with hindlimb ischemia, the coated FGF-2 triggered recovery in as little as seven days. The team's results, recently published in the Proceedings of the National Academy of Sciences, demonstrate that enhanced cell binding of the growth factor leads to a boost in division and proliferation of new vascular cells.

Laser doppler image of rat's leg prior to treatment (left) and seven days after injection of the coated FGF-2 (right)

"We hope this research will increase our understanding of how tissues become resistant to revascularization therapies and may lead to more effective treatments for this widespread and debilitating disease," Baker said. That's a shot of welcome news, indeed, for MID patients whose future may now offer a less-invasive option to the surgery they otherwise would surely have faced.

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