Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia. Am J Physiol Heart Circ Physiol 2013 Jan 15;304(2):H328-36



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-84872401697   9 Citations


Hemolysis can saturate the hemoglobin (Hb)/heme scavenging system, resulting in increased circulating cell-free Hb (CF-Hb) in hereditary and acquired hemolytic disease. While recent studies have suggested a central role for intravascular hemolysis and CF-Hb in the development of vascular dysfunction, this concept has stimulated considerable debate. This highlights the importance of determining the contribution of CF-Hb to vascular complications associated with hemolysis. Therefore, a novel Hb-binding peptide was synthesized and linked to a small fragment of apolipoprotein E (amino acids 141-150) to facilitate endocytic clearance. Plasma clearance of hE-Hb-b10 displayed a rapid phase t(1/2) of 16 min and slow phase t(1/2) of 10 h, trafficking primarily through the liver. Peptide hE-Hb-B10 decreased CF-Hb in mice treated with phenylhydrazine, a model of acute hemolysis. Administration of hE-Hb-B10 also attenuated CF-Hb in two models of chronic hemolysis: Berkeley sickle cell disease (SS) mice and mice with severe hereditary spherocytosis (HS). The hemolytic rate was unaltered in either chronic hemolysis model, supporting the conclusion that hE-Hb-B10 promotes CF-Hb clearance without affecting erythrocyte lysis. Interestingly, hE-Hb-B10 also decreased plasma ALT activity in SS and HS mice. Although acetylcholine-mediated facialis artery vasodilation was not improved by hE-Hb-B10 treatment, the peptide shifted vascular response in favor of NO-dependent vasodilation in SS mice. Taken together, these data demonstrate that hE-Hb-B10 decreases CF-Hb with a concomitant reduction in liver injury and changes in vascular response. Therefore, hE-Hb-B10 can be used to investigate the different roles of CF-Hb in hemolytic pathology and may have therapeutic benefit in the treatment of CF-Hb-mediated tissue damage.

Author List

Hanson MS, Xu H, Flewelen TC, Holzhauer SL, Retherford D, Jones DW, Frei AC, Pritchard KA Jr, Hillery CA, Hogg N, Wandersee NJ


Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Anemia, Hemolytic
Anemia, Sickle Cell
Apolipoproteins E
Chronic Disease
Disease Models, Animal
Mice, Inbred C57BL
Mice, Transgenic
Nitric Oxide
Peptide Fragments
Protein Binding
Protein Transport
Spherocytosis, Hereditary
Vasodilator Agents
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a