Ischemic insult to an organ or skeletal tissue and subsequent reperfusion is a common and important problem in many clinical conditions. Ischemia/Reperfusion (I/R) injury affects more than 5 million Americans each year following heart attack, stroke, limb or other forms of peripheral ischemia, hypovolemic shock and sepsis. These serious and often fatal conditions are difficult to treat and improved clinical tools are required. In many cases, thrombolytics represent the only means of pharmacological treatment; however, they are associated with a narrow window of therapeutic opportunity. Furthermore, although thrombolytics are useful in re-establishing blood flow, they do little to reduce the ischemic damage that results from occlusion and that is exacerbated by the process of reperfusion. The total market for these conditions is worth over $5 billion. This, combined with the need for improved clinical options, represents a considerable driving force for the development of agents able to prevent the effects of I/R injury, rather than simply shortening the period of ischemia, as is the case for the thrombolytics. The development of I/R injury is multi-factorial but the wave of inflammatory mediators that passes into organs upon reperfusion often causes as much, if not more, damage that the initial period of ischemia. Hence anti-inflammatory agents or approaches designed to prevent the accumulation of inflammatory cells, in particular neutrophils, underlie one approach to ischemic insult. High density lipoproteins (HDLs) inhibit the cytokine-induced expression of endothelial cell adhesion molecules both in vitro and in vivo. British-based researchers have thus recently examined the ability of HDLs to mediate a functional anti-inflammatory effect by measuring their ability to prevent neutrophil adhesion and transmigration in vitro. Treatment of human endothelial cell cultures with physiologic concentrations of HDLs dramatically inhibited neutrophil binding. As a result, HDLs prevented the severe disruption of tissue architecture and cellular infiltration in organs that are commonly susceptible to I/R and which are ultimately responsible for the high levels of mortality associated this group of conditions. This use of HDLs is available as a licensing or co-development opportunity and may be of interest to companies with a focus on inflammation or cardiovascular disease.

Entry date September, 2002

Adapted from Cockerill et al, FASEB J 2001 Sep;15(11):1941-52

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