Vascular Biology and Atherothrombosis

In atherosclerosis, raised structures called plaques form in the lining of arteries by the accumulation of white blood cells, fats and connective tissue in the blood vessel wall. The force of flowing blood and other factors can disrupt the structure of these plaques, exposing their contents to blood. Blood contacting the exposed plaque contents is stimulated to clot, much like blood contacting tissues after an injury. The abnormal blood clots, known as “thrombi”, that form over ruptured plaques in an artery can block the flow of blood. When such blockages occur in arteries that supply the heart, heart attacks result. Clotting in the arteries that supply the brain cause one type of stroke.

Scientists focused on vascular biology and atherothrombosis are working to uncover the molecular and cellular mechanisms of atherosclerosis and thrombosis to understand how normal processes that protect us from infection and bleeding can go awry to cause disease, with the goal of developing methods to derail atherosclerosis and prevent thrombosis.

Physicians studying how plaque forms and ruptures to cause heart attack and stroke interact with molecular and cell biologists examining how white blood cells normally move in and out of blood vessels and remodel tissues. These same researchers will work with molecular imaging experts to develop ways of visualizing active plaque by MRI or other noninvasive techniques. This technology will help them identify new methods of detecting the formation of plaque and of following the processes involved so that scientists can more efficiently test hypotheses regarding plaque development and physicians can better assess risk and intervene.

Chemists are currently working to identify the substances that cause inflammation in the blood vessel wall. These scientists will work with immunologists and others to determine how these substances regulate cellular behaviors. Intriguingly, it appears that substances from oxidized lipids may mimic invading microbes and activate normal host defense processes at an inappropriate place and time. Scientists in this field will develop antibodies that clear candidate activating chemicals from the blood or that block their action on cells, then collaborate with animal model experts to determine whether such antibodies will prevent or decrease plaque formation. Such work might lead to new drugs to treat atherosclerosis and even to a vaccine to prevent it.

Biochemists and cell biologists studying basic mechanisms of thrombosis will work closely with network engineers to examine how changes in the levels of individual clotting factors impact the efficiency of the clotting system as a whole. Because clotting factor levels vary from individual to individual, these studies will help researchers predict which individuals are most susceptible to thrombosis.

These same scientists will work with molecular imaging experts to develop methods of detecting thrombi and new targets for preventive therapy. They will also interact with geneticists to devise gene-based approaches for identifying patients at risk for thrombosis. Finally, they will work with physicians interested in the prevention and treatment of acute ischemic syndromes to explore whether small asymptomatic thrombi at a disrupted plaque or other markers of subclinical events might be detected and used to identify individuals at risk for heart attack and stroke in the near future.