title: The Mechanism of Proinflammatory HDL Generation in Sickle Cell Disease Is Linked to Cell-Free Hemoglobin via Haptoglobin.
abstract: In sickle cell disease (SCD), the inflammatory properties of high-density lipoprotein (HDL) can be changed by cell-free hemoglobin (Hb), which is released into the blood during hemolysis. Hb in the plasma of SCD patients or mice can bind with HDL specifically inducing an inflammatory reaction. In our study, we found increased amounts of inflammatory factor proteins in the chronic oxidative state of SCD with higher levels of Hb, haptoglobin (Hp) and hemopexin (Hx) in the apolipoprotein A-I (ApoA-1) particles of HDL and the role of HDL is changed from being anti-inflammatory to proinflammatory. Our results also suggest Hp and Hx, the scavengers of Hb in HDL, are positively associated with inflammatory levels in SCD patients. HDL retained its inflammatory inhibition role in Hp-/- mice, with less Hb accumulation. Hx may further prevent inflammatory reaction because its level will be even higher when lack of Hx. We therefore demonstrated that Hp is indispensable during the process whereby Hb associates with HDL and plays a clear proinflammatory role. Therefore, it is essential to break the binding between Hb and Hp for treatment. The dissociation of Hb/Hp/Hx complexes may also play an important role in the study of other inflammatory angiogenesis-related diseases.
authors.affiliation: Geriatric Department Qilu Hospital of Shandong Univeristy; Shandong Key Laboratory of Proteomics, Jinan 250012, Shandong, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ji
authors.affiliation: Clinical Laboratory, Qilu Hospital of Shandong Univeristy, Jinan 250012, Shandong, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: ICU, The Affiliated Hospital of Qiingdao University, Qingdao 266012, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.affiliation: Cardiology Department, Qilu Hospital of Shandong Univeristy, Jinan 250012, Shandong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.affiliation: Geriatric Department Qilu Hospital of Shandong Univeristy; Shandong Key Laboratory of Proteomics, Jinan 250012, Shandong, China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Wang
authors.affiliation: Pharmacological Laboratory, Qilu Hospital of Shandong Univeristy, Jinan 250012, Shandong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Geriatric Department Qilu Hospital of Shandong Univeristy; Shandong Key Laboratory of Proteomics, Jinan 250012, Shandong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Endocrinology Department, Qilu Hospital of Shandong Univeristy, Jinan 250012, Shandong, China.
authors.forename: Lingshu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Geriatric Department Qilu Hospital of Shandong Univeristy; Shandong Key Laboratory of Proteomics, Jinan 250012, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Geriatric Department Qilu Hospital of Shandong Univeristy; Shandong Key Laboratory of Proteomics, Jinan 250012, Shandong, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Gao
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D005260:Female; D006242:Haptoglobins / Q000378:metabolism*; D006403:Hematologic Tests / Q000379:methods; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis / Q000502:physiology; D006466:Hemopexin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction
chemical_list: D016632:Apolipoprotein A-I; D006242:Haptoglobins; D006454:Hemoglobins; D008075:Lipoproteins, HDL; C035492:haptoglobin-hemoglobin complex; D006466:Hemopexin