Oxidized Low-Density Lipoprotein and Atherosclerosis

Abstract

Chance and serendipity play major roles in the history of science. Too often, though, their contributions do not show up in formal publications. We all tend to shape history according to the styles of the times and according to our own biases. Acknowledged or unacknowledged, there is a tendency to want the scientific “story” to be neat and more or less linear. The genesis of the oxidized low-density lipoprotein (OxLDL) hypothesis owed a great deal to happenstance, but that may not be readily apparent from the formal articles. We take this opportunity to tell the whole story, at least as we remember it. Several apparently unrelated events occurring at about the same time in Oslo, Norway; in Cleveland, Ohio; in La Jolla, California; in New York, New York; and in Dallas, Texas converged to lay the groundwork for the hypothesis that oxidative modification of LDL might be important in atherogenesis. Later developments regarding the relationship between OxLDL and the immune system in atherogenesis, again, were often smiled on by chance and serendipity. In 1979, a young Norwegian researcher, Tore Henriksen, got in touch with our laboratory asking whether he could come to La Jolla to learn more about lipoproteins. He and his colleagues in Oslo had observed that under certain conditions, LDL was highly toxic for endothelial cells in culture, leading to cell death in just 24 hours.1 Almost simultaneously and independently, Chisolm and coworkers in Cleveland made very similar observations.2 Both groups noted that addition of whole serum or purified high-density lipoprotein to the medium completely prevented the toxic effects of the LDL, but the mechanism(s) involved remained unclear. Henriksen arrived in La Jolla in the summer of 1980 and demonstrated to us how drastically LDL affected the cultured cells. We agreed that the phenomenon was worth …