Reduced peripheral blood superoxide dismutase 2 expression in sickle cell disease
- 174 Downloads
Sickle cell disease (SCD), a hereditary form of chronic hemolytic anemia, is characterized by acute vascular occlusion and chronic complications as pulmonary hypertension (PH), a hallmark of higher mortality. This study aimed to determine peripheral blood expression of superoxide dismutase 2 (SOD2), a major mitochondrial antioxidant enzyme in SCD patients on the mRNA level and compared it with SOD2 expression in healthy individuals. It also aimed to detect possible differences in SOD2 expression among patients with/without specific SCD complications and to detect possible correlations with patient laboratory parameters. SOD2 mRNA levels were significantly lower in SCD patients in comparison with controls and correlated with red blood cell count, reticulocyte count, platelet count, C-reactive protein, ferritin, and brain natriuretic peptide values. SCD patients with echocardiographic indications of PH featured significantly reduced SOD2 expression in comparison with patients without such indications. Consequently, SOD2 expression emerges as a potential biomarker of PH in SCD being a link among hemolysis, inflammation, iron overload, oxidative stress, and SCD cardiopathy.
KeywordsSickle cell disease Superoxide dismutase SOD2 MnSOD Pulmonary hypertension
The study was supported by the Program: “IKY fellowships of excellence for postgraduate studies in Greece-Siemens Program.”
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 6.Gizi A, Papassotiriou I, Apostolakou F, Lazaropoulou C, Papastamataki M, Kanavaki I, Kalotychou V, Goussetis E, Kattamis A, Rombos I, Kanavakis E (2011) Assessment of oxidative stress in patients with sickle cell disease: the glutathione system and the oxidant-antioxidant status. Blood Cell Mol Dis 46:220–225CrossRefGoogle Scholar
- 7.Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A et al (2016) 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 37:67–119CrossRefGoogle Scholar
- 9.Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaïci A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G (2011) A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med 365:44–53CrossRefGoogle Scholar
- 12.Farias ICC, Mendonça-Belmont TF, da Silva AS, do ÓKP, Ferreira F, Medeiros FS, da Silva Vasconcelos LR, Bezerra MAC, da Silva Araújo A, de Moura PMMF et al (2018) Association of the SOD2 polymorphism (Val16Ala) and SOD activity with vaso-occlusive crisis and acute splenic sequestration in children with sickle cell anemia. Mediterr J Hematol Infect Dis 10:e2018012CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Klings ES, Machado RF, Barst RJ, Morris CR, Mubarak KK, Gordeuk VR, Kato GJ, Ataga KI, Gibbs JS, Castro O, Rosenzweig EB, Sood N, Hsu L, Wilson KC, Telen MJ, Decastro LM, Krishnamurti L, Steinberg MH, Badesch DB, Gladwin MT (2014) An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease. Am J Respir Crit Care Med 189:727–740CrossRefPubMedPubMedCentralGoogle Scholar
- 18.de Oliveira Filho RA, Silva GJ, de Farias Domingos I, Hatzlhofer BL, da Silva Araújo A, de Lima Filho JL, Bezerra MA, Martins DB, de Araújo RF (2013) Association between the genetic polymorphisms of glutathione S-transferase (GSTM1 and GSTT1) and the clinical manifestations in sickle cell anemia. Blood Cells Mol Dis 51:76–79CrossRefPubMedGoogle Scholar
- 19.Damy T, Bodez D, Habibi A, Guellich A, Rappeneau S, Inamo J, Guendouz S, Gellen-Dautremer J, Pissard S, Loric S, Wagner-Ballon O, Godeau B, Adnot S, Dubois-Randé JL, Hittinger L, Galactéros F, Bartolucci P (2016) Haematological determinants of cardiac involvement in adults with sickle cell disease. Eur Heart J 37:1158–1167CrossRefPubMedGoogle Scholar
- 20.Maitra P, Caughey M, Robinson L, Desai PC, Jones S, Nouraie M, Gladwin MT, Hinderliter A, Cai J, Ataga KI (2017) Risk factors for mortality in adult patients with sickle cell disease: a meta-analysis of studies in North America and Europe. Haematologica. 102:626–636CrossRefPubMedPubMedCentralGoogle Scholar