A Lifesaving Legacy

The importance of angiogenesis in health and disease is also leading to new insights for obesity. It turns out that fat, like tumors, also relies on a blood supply to grow. In some of his last work, Folkman and his colleagues found that antiangiogenesis drugs caused dramatic weight loss in obese mice by reducing the blood supply to fat cells. I found it especially interesting that these mice lost weight even when their food intake was unchanged, raising new possibilities in obesity research. Imagine if, one day, an antiangiogenic pill enabled you to lose weight without eating less food!

In some circumstances, angiogenesis can be healing. Therapeutic angiogenesis is a new approach in medicine whereby doctors stimulate blood vessels to promote repair and healing. For example, when arteries that feed your brain and heart get clogged with atherosclerosis, angiogenesis causes new blood vessels to grow around these blocked arteries to help prevent a heart attack or a stroke. These new blood vessels, called collaterals, are stimulated by regular exercise. 

In addition to exercise, scientists are now finding that they can enhance angiogenesis in the arteries that feed the heart by transplanting cells from the subcutaneous fat into the heart. Fat tissue contains angiogenic stem cells (called adipose stromal cells, or ASCs), which increase the blood supply to fat cells, promoting obesity. Cardiologists have discovered that by removing fat using liposuction, it is possible to harvest these adult stem cells and implant them into the heart, where they grow natural bypass channels, at least in mice. Should this prove effective in humans, one day we may see overweight patients with coronary disease treated by both the plastic surgeon and interventional cardiologist, then maintained on an antiangiogenic weight-control diet. 

Besides residing in fat, angiogenic stem cells are stored in our bone marrow, called into action whenever they are needed for cardiovascular regeneration. Clinical trials are now underway to harvest these bone-marrow-derived angiogenic stem cells and transplant them into the heart to create a better blood supply, as an alternative to bypass surgery--a recent randomized controlled trial in humans showed some encouraging results. Products are now being developed to treat coronary disease and peripheral arterial disease using genes, proteins and adult stem cells that stimulate angiogenesis in diseased tissue. Some medical researchers even believe that angiogenic stem-cell therapy may be a key to regenerating the heart, brain, liver, nerves and other vital organs.

Also, Folkman's research led to our understanding that wounds require new blood vessels to heal. In 1997, the FDA approved a topical angiogenesis-stimulating gel called Regranex that heals foot ulcers in diabetics. A 2005 study of 24,898 diabetic patients showed that patients who received this drug had a 30 percent reduced risk of having their leg amputated. 

All of these remarkable advances emerged from the vision, perseverance and determination of one man, Dr. Judah Folkman, whose keen powers of observation, ability to think beyond the accepted beliefs and ability to inspire others led him to leave one of the biggest footprints in modern medicine. 

© 2008