Intraplaque hemorrhage.
Intraplaque hemorrhage is a common feature of atherosclerotic plaques and is considered one of the identifying features of complex lesions preceding acute ischemic events. The cause of intraplaque hemorrhage is most often secondary to rupture of neovessels, which have invaded the plaque. However, inflammation and metabolic factors such as diabetes may also precipitate hemorrhage from mature microvessels by damaging the endothelium. The mechanism by which hemorrhage destabilizes the plaque is in large part secondary to the action of hemoglobin released from red blood cells at the site of the hemorrhage. Hemoglobin is a potent pro-inflammatory agent by virtue of its ability to promote formation of ROS. The major defense mechanism against the toxic effects of extracorpuscular hemoglobin is the protein haptoglobin, which tightly binds to hemoglobin and prevents it from catalyzing oxidative reactions. There exists a common allelic polymorphism in the haptoglobin gene, which has recently been strongly associated with the risk of cardiovascular disease in multiple independent cohorts. The protein products of the two different haptoglobin alleles differ in their ability to serve as an antioxidant against hemoglobin and also to activate the CD163 receptor. This review presents a unifying hypothesis whereby the haptoglobin genotype is proposed to modulate the response to intraplaque hemorrhage and thereby play a fundamental role in determining the morphological and metabolic features of complex plaques preceding acute ischemic events.
Levy
A P
AP
Bruce Rappaport Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. alevy@tx.technion.ac.il
Moreno
P R
PR
D000818:Animals; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006470:Hemorrhage / Q000235:genetics / Q000473:pathology*; D006801:Humans; D018384:Oxidative Stress
D006242:Haptoglobins; D006454:Hemoglobins