David Gutterman: Focusing on the Little Things Leads to Big Discoveries

In research, as in life, we often focus our attention on the big things. For example, the large arteries in the heart are probably some of the most well-studied parts of the human body, but the majority of our circulatory system is made up of much smaller blood vessels, including arterioles that are only a little thicker than a human hair. For David Gutterman, MD, it is that attention to the little things that has led to unexpected discoveries and major insights into cardiovascular function in humans. Gutterman, who is Professor and Senior Associate Director of the Medical College of Wisconsin Cardiovascular Center, has focused his research on understanding the microcirculatory system and how it dynamically regulates blood flow to feed our organs. He takes the unusual approach of using primarily human tissue in his research. The microcirculatory system is controlled by the delicate balance of chemicals released from the endothelium, the innermost lining of all vessels. Two of these chemicals play a major role, namely, NO and hydrogen peroxide. In healthy adults, blood flow or chemical agonists stimulate NO release, which causes vasodilation. NO also modulates oxygen consumption and prevents inflammation and atherosclerosis. In contrast, blood flow in patients with heart disease releases hydrogen peroxide instead of NO. Like NO, hydrogen peroxide is a dilator substance, but it can also be proinflammatory and promote atherosclerosis. Discovery of this switch from NO to hydrogen peroxide set off a flurry of studies to understand why the shift occurs and how to prevent it as a possible means of treating cardiovascular disease. David Gutterman Gutterman identified 2 unexpected compounds, TERT (the catalytic subunit of telomerase) and ceramide, that play opposing roles in the switch between NO and hydrogen peroxide.1–3 In its primary role, TERT acts in the nucleus to …