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Hypocholesterolemia and dysregulated production of angiopoietin-like proteins in sickle cell anemia patients

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Vendrame, Felipe [1] ; Olops, Leticia [1] ; Olalla Saad, Sara Teresinha [1] ; Ferreira Costa, Fernando [1] ; Yotsumoto Fertrin, Kleber [1, 2]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Campinas UNICAMP, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil
[2] Univ Washington, Div Hematol, Seattle, WA 98195 - USA
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: CYTOKINE; v. 120, p. 88-91, AUG 2019.
Citações Web of Science: 0

Angiopoietin-like proteins (ANGPTL) are responsible for inhibiting lipoprotein lipase activity, and ANGPTL3 and ANGPTL4 deficiencies have been shown to lower lipoprotein levels in animal models and in humans carrying loss-of-function mutations. Sickle cell anemia (SCA) is a hereditary hemolytic anemia characterized by vaso-occlusive crises and end-organ damage, which is curiously associated with hypocholesterolemia and a low incidence of atherosclerosis, whose underlying mechanisms are unclear. We hypothesized that ANGPTL3 and ANGPTL4 dysregulation is responsible for the hypolipidemic phenotype in SCA. We measured circulating concentrations of ANGPTL3 and ANGPTL4 and correlated them with hemolytic biomarkers and lipoproteins in 40 patients with SCA and 30 control individuals. The association between hemolysis and low cholesterol levels in SCA was confirmed along with surprisingly higher levels of ANGPTL3 and ANGPTL4 in SCA patients than in controls. ANGPTL3 correlated with hemolysis markers LDH and reticulocyte counts, while ANGPTL4 did not. Our data show a paradoxical increase in production of ANGPTL3 and ANGPTL4 in SCA, which would be expected to cause hyperlipidemia, due to increased inhibition of lipoprotein lipase. ANGPTL3, exclusively produced by the liver, correlated with hemolysis markers, suggesting a possible hepatic response to hemolysis. Further functional studies and replication in larger cohorts are warranted to investigate the dysregulation of lipid metabolism in SCA. (AU)

Processo FAPESP: 14/00984-3 - Doenças dos glóbulos vermelhos: fisiopatologia e novas abordagens terapêuticas
Beneficiário:Fernando Ferreira Costa
Linha de fomento: Auxílio à Pesquisa - Temático