Restoring HOmeostasis: is heme oxygenase-1 ready for the clinic?
Inflammation and immunity result in a wide range of disease processes, including atherosclerosis, vascular thrombosis and sepsis. Heme oxygenase-1 (HO-1) is a key enzyme that is integral to the temporal and spatial regulation of the host response and, together with its products carbon monoxide (CO) and bilirubin, is crucial for maintaining homeostasis and the preservation of function and life. An increasing number of reports demonstrates that HO-1, CO and bilirubin regulate the immune response. As CO and bilirubin enter clinical trials, there are obstacles to be addressed before their full therapeutic potential can be achieved. In this article, we delineate the challenges that lie ahead regarding toxicity, pharmacokinetics and mechanisms of action to be able to take full advantage of the powerful cytoprotective properties of these agents for clinical benefit.
Scott
Jeffrey R
JR
Transplant Research Center, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Chin
Beek Y
BY
Bilban
Martin H
MH
Otterbein
Leo E
LE
D050197:Atherosclerosis / Q000503:physiopathology; D001663:Bilirubin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001664:Biliverdine / Q000494:pharmacology* / Q000627:therapeutic use; D002248:Carbon Monoxide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019610:Cytoprotection / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020011:Protective Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018805:Sepsis / Q000503:physiopathology; D013927:Thrombosis / Q000503:physiopathology
D020011:Protective Agents; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D001664:Biliverdine; D001663:Bilirubin