Role of free hemoglobin in 8-iso prostaglandin F2-alpha synthesis in chronic renal failure and its impact on CD163-Hb scavenger receptor and on coronary artery endothelium.
Free hemoglobin (Hb) during autoxidation increases 8-iso-prostaglandin-F2-alpha (8-isoprostane) formation in vitro. Because 8-isoprostane and plasma Hb are elevated in chronic renal failure (CRF), we evaluated the role of Hb in this isoprostane synthesis in vivo. By monitoring correlations between Hb, haptoglobin (Hp), CD163-Hb-scavenger receptor, and 8-isoprostane that is known to induce CD163 shedding, we examined whether 8-isoprostane blocks Hb catabolism in CRF. Additionally, by studying the effect of 8-isoprostane on human coronary artery endothelium (HCAEC) in vitro and its impact on intercellular adhesion molecule-1 (ICAM-1) in vivo, we tested its role in promotion of cardiovascular events in CRF. Twenty-two never-dialyzed CRF patients and 18 control patients were screened for renal function, plasma and urine 8-isoprostane, and plasma Hb, Hp, thiobarbituric-acid-reactants (TBARS), C-reactive-protein (CRP), and soluble (s) ICAM-1 and sCD163. HCAEC exposed to 8-isoprostane were tested for ICAM-1 and apoptosis. In CRF, urine 8-isoprostane was significantly elevated and correlated with free-Hb and TBARS. The increased free-Hb, Hp, and sCD163 in CRF suggested 8-isoprostane-mediated suppression of Hb catabolism through CD163 receptor shedding. 8-Isoprostane enhanced ICAM-1 expression and apoptosis in HCAEC. CRF patients showed elevated sICAM-1. In conclusion, free-Hb, via 8-isoprostane, paradoxically blocks its own catabolism. Free-Hb and/or 8-isoprostane may intensify cardiovascular events in CRF.
Simoni
Jan
J
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Simoni
Grace
G
Griswold
John A
JA
Moeller
John F
JF
Tsikouris
James P
JP
Khanna
Apurv
A
Roongsritong
Chanwit
C
Wesson
Donald E
DE
D000419:Albuminuria / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000652:urine; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006242:Haptoglobins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D017392:Thiobarbituric Acid Reactive Substances; D018799:Intercellular Adhesion Molecule-1; C075750:8-epi-prostaglandin F2alpha; D002097:C-Reactive Protein; D003404:Creatinine; D015237:Dinoprost; D010100:Oxygen