{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:21:45Z","timestamp":1773660105910,"version":"3.50.1"},"reference-count":60,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,1,15]]},"abstract":"<jats:p>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\u2013150) to facilitate endocytic clearance. Plasma clearance of hE-Hb-b10 displayed a rapid phase t<jats:sub>1\/2<\/jats:sub>of 16 min and slow phase t<jats:sub>1\/2<\/jats:sub>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.<\/jats:p>","DOI":"10.1152\/ajpheart.00500.2012","type":"journal-article","created":{"date-parts":[[2012,11,3]],"date-time":"2012-11-03T04:27:40Z","timestamp":1351916860000},"page":"H328-H336","source":"Crossref","is-referenced-by-count":14,"title":["A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia"],"prefix":"10.1152","volume":"304","author":[{"given":"Madelyn S.","family":"Hanson","sequence":"first","affiliation":[{"name":"Department of Biophysics and Redox Biology Program, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Translational Vascular Biology Program, Medical College of Wisconsin, Milwaukee, 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