Abstract

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.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.