Intersecting Vectors of Basic Science Research and Clinical Medicine: LOX-1?

The decrease in cardiovascular events over the past 30 years has been clear (1). Such improvements in clinical outcomes have been matched, if not fueled, by advances in understanding basic mechanisms of atherosclerosis and its complications (2).Despite such progress, major hurdles persist. Cardiovascular complications remain late-stage events; the pathologic process of atherosclerosis is present years if not decades before myocardial infarction (MI)1 or stroke occurs. As such, many individuals present with cardiovascular disease at the time of a life-threatening cardiovascular event, with a significant percentage not surviving this initial insult or doing so with compromised quality of life and productivity. Among forms of cardiovascular disease, the gains seen in coronary heart disease, like acute MI mortality, have outstripped the trends for stroke (1). Indeed, in some countries, the incidence of stroke has been increasing. Debate has continued around whether various aspects of the lipid profile are predictive of stroke and whether nonstatin cholesterol-lowering therapy decreased cerebrovascular events. Combined, these issues represent distinct vectors: (1) ever-increasing knowledge into mechanisms and specific mediators of atherosclerosis and its complications and (2) the need for earlier, more sensitive detection and prediction of cardiovascular risk, especially as related to stroke.In this issue, Inoue et al. (3) present data relevant to the prospect that advances in science might be applied to the prediction of cardiovascular disease. A central tenet of atherosclerosis has been the concept that LDL undergoes modification into oxidized LDL (oxLDL) in tissues like the arterial wall. Uptake of oxLDL by macrophages and other vascular cells incites a cascade of events that promote inflammation, atherosclerosis, and eventually plaque rupture. A major advance in this area came with the identification of the lectin-like oxidized LDL receptor 1 (LOX-1) that, upon activation by ox-LDL binding, induces multiple proatherosclerotic responses in endothelial cells …