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PMID: 7680672 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.

The Journal of clinical investigation ·Vol. 91 ·No. 3 ·1993-03-00 ·Pages 977-85

Cid MC, Grant DS, Hoffman GS, Auerbach R, Fauci AS, Kleinman HK

Abstract

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.

MeSH Terms
Amino Acid Sequence Angiogenesis Inducing Agents/analysis,blood,pharmacology Animals Cell Differentiation/drug effects Cells, Cultured Endothelium, Vascular/cytology,drug effects Haptoglobins/analysis,pharmacology Humans Mice Mice, Nude Neovascularization, Pathologic/pathology Reference Values Umbilical Veins Vasculitis/blood,physiopathology
Chemicals
Angiogenesis Inducing Agents Haptoglobins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cid M C
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Grant D S
Hoffman G S
Auerbach R
Fauci A S
Kleinman H K
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI116319
Published
1993-03-00
Pages
977-85
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC288050
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI116319 PMC Full Text View journal details
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