In many cardiovascular diseases, including heart attack, cerebral stroke, and even in individuals with just risk factors for cardiovascular disease, such as smokers or individuals with chronic infections, a set of inflammatory mediators can be detected in the blood circulation. These inflammatory mediators are not detected to any significant degree in young health individuals without cardiovascular complications and individuals without cardiovascular risk factors. The inflammatory mediators are detectable in blood plasma and may be present long before actual serious complications arise which may require interventions and hospitalization. The inflammatory mediators produce cell activation in large and small blood vessels, which leads to many forms of cell and tissue dysfunctions and even frank cell death. These mediators produce a form of noninfectious inflammation that can cause many complications, such as lesions in the large arteries or occlusion of blood vessels in the microcirculation. But the source of these inflammatory mediators and their molecular identity has remained unknown. We are focused on a series of research projects that is designed to find the origin of these inflammatory mediators. It is one of the fascinating detective stories in medicine. Identification of these inflammatory mediators will provide the knowledge necessary to facilitate early intervention and dramatically improve our ability to develop new approaches for minimization of cardiovascular disease.

Our research program is focused on physiological shock, a condition with high mortality and very difficult to manage successfully. In shock especially high levels of the inflammatory mediators can be detected and healthy organs may fail and die in rapid succession. A number of researchers in our laboratory have made contributions to this problem. Dr. Erik Kistler has discovered a source for the activating factor derived from a unique and also surprising source. Our collaborator, Dr. Toni Hugli of the La Jolla Institute for Molecular Medicine, and Ms. Anasthasia Sofianos identified a way to purify the inflammatory mediators. Dr. Hiroshi Mitsuoka has discovered a way to block the production of the activating factors in shock, a procedure that prevents organ failure in experimental models of shock. Dr. Florian Fitzal examined the utility of this new intervention in septic shock, and especially important clinical problem. Mr. Alexander Penn, a graduate student in Bioengineering, studies the molecular structure of the inflammatory mediators and their mode of action on cells. - You may stay tuned for further developments.

Electron micrograph of neutrophil migration across venular endothelium (EN) with pseudopod formation (PP) underneath the endothelium.