Treating myocardial ischemia-reperfusion injury by targeting endothelial cell transcription.
Exacerbation of, rather than improvement in, a hypoxic injury after reperfusion of ischemic tissues is recognized as the specific clinicopathologic entity referred to as ischemia/reperfusion (I/R) injury. Arguably, one of the most common forms of I/R injury occurs during cardiac surgery, which has a mandatory period of myocardial ischemia required to allow surgery in a bloodless, motionless field, followed by coronary artery reperfusion after removal of the aortic cross-clamp. In this review, we examine the endothelial cell activation phenotype that initiates and propagates myocardial I/R injury. Emphasis is given to the biology of one transcription factor, NF-kappaB, that has the principal role in the regulation of many endothelial cell genes expressed in activated endothelium. NF-kappaB-dependent transcription of endothelial cell genes that are transcribed in response to I/R injury may be a favorable approach to preventing tissue injury in the setting of I/R. Elucidating safe and effective therapy to inhibit transcription of endothelial cell genes involved in promoting injury after I/R injury may have wide applicability to the patients with heart disease and other forms of I/R injury.
Boyle
E M
EM
Department of Surgery, University of Washington, Seattle 98195-6310, USA.
Canty
T G
TG
Morgan
E N
EN
Yun
W
W
Pohlman
T H
TH
Verrier
E D
ED
D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000503:physiopathology; D016328:NF-kappa B / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics; D018180:Thrombomodulin / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
D016328:NF-kappa B; D018180:Thrombomodulin