Impaired deformability of erythrocytes in diabetic rat and human: investigation by the nickel-mesh-filtration technique

Springer Science and Business Media LLC - Tập 25 - Trang 18-26 - 2011
K. Saito1, Y. Kogawa2, M. Fukata2, K. Odashiro2, Toru Maruyama3, K. Akashi2, T. Fujino4
1BOOCS Clinic, Fukuoka, Japan
2Department of Medicine, Kyushu University, Fukuoka, Japan
3Institute of Health Science, Kyushu University, Kasuga, Japan
4Institute of Rheological Function of Foods Co. Ltd, Hisayama, Japan

Tóm tắt

Comprehensive research to quantify the deformability of erythrocytes in diabetic animals and humans has been lacking. The objective of this study was to compare the impairment of erythrocyte deformability in diabetic rats and patients by use of the same rheologic method. Deformability was investigated in streptozotocin-induced diabetic rats and diabetic patients, by using the highly sensitive and quantitative nickel-mesh-filtration technique. Erythrocyte filterability (whole-cell deformability) was defined as flow rate of hematocrit-adjusted erythrocyte suspension relative to that of saline (%). Hematological and biochemical data for diabetic rats did not differ from those for age-matched control rats except for hyperglycemia and malnutrition. Erythrocyte filterability for diabetic rats was significantly lower than that for control rats (69.4 ± 10.1%, n = 8, compared with 83.1 ± 4.2%, n = 8; p < 0.001). Likewise, erythrocyte filterability for diabetic patients was significantly impaired compared with that for controls (87.6 ± 3.4%, n = 174, compared with 88.6 ± 2.1%, n = 51; p = 0.046). Stepwise multiple regression analysis revealed that this impairment was mostly attributable to associated obesity (BMI, p = 0.029) and glycemic stress (HbA1c(JDS), p = 0.046). We therefore conclude that erythrocyte filterability is commonly impaired in diabetic rats and in humans. Moreover, metabolic risk accumulation further impairs erythrocyte filterability, resulting in derangement of the microcirculation.

Tài liệu tham khảo

Caimi G, Presti RL. Techniques to evaluate erythrocyte deformability in diabetes mellitus. Acta Diabetol. 2004;41:99–103. Rodgers GP, Dover GJ, Uyesaka N, Noguchi CT, Schechter AN, Nienhuis AW. Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. N Engl J Med. 1993;328:73–80. Hiruma H, Noguchi CT, Uyesaka N, Schechter AN, Rodgers GP. Contributions of sickle hemoglobin polymer and sickle cell membranes to impaired filterability. Am J Physiol. 1995;268:H2003–8. Oonishi T, Sakashita K, Uyesaka N. Regulation of red blood cell filterability by Ca2+ influx and cAMP-mediated signaling pathways. Am J Physiol. 1997;273:C1828–34. Ariyoshi K, Maruyama T, Odashiro K, Akashi K, Fujino T, Uyesaka N. Impaired erythrocyte filterability of spontaneously hypertensive rats: investigation by nickel mesh filtration technique. Circ J. 2010;74:129–36. Ejima J, Ijichi T, Ohnishi Y, Maruyama T, Kaji Y, Kanaya S, et al. Relationship of high-density lipoprotein cholesterol and red blood cell filterability: cross-sectional study of healthy subjects. Clin Hemorheol Microcirc. 2000;22:1–7. Arai K, Iino M, Shio H, Uyesaka N. Further investigations of red cell deformability with nickel mesh. Biorheology. 1990;27:47–65. Nakamura T, Hasegawa S, Shio H, Uyesaka N. Rheologic and pathophysiologic significance of red cell passage through narrow pores. Blood Cells. 1994;20:151–65. Mohandas N, Chasis JA. Red cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids. Semin Hematol. 1993;30:171–92. Yang ZC, Xia K, Wang L, Jia SJ, Li D, Zhang Z, et al. Asymmetric dimethylarginine reduced erythrocyte deformability in streptozotocin-induced diabetic rats. Microvasc Res. 2007;73:131–6. Djemli-Shipkolye A, Raccah D, Pieroni G, Vague P, Coste TC, Gerbi A. Differential effect of omega3 PUFA supplementations on Na, K-ATPase and Mg-ATPase activities: possible role of the membrane omega6/omega3 ratio. J Membr Biol. 2003;191:37–47. Ramesh B, Pugalendi KV. Influence of umbelliferone on membrane-bound ATPases in streptozotocin-induced diabetic rats. Pharmacol Rep. 2007;59:339–48. Diamantopoulos EJ, Kittas C, Charitos D, Grigoriadou M, Ifanti G, Raptis SA. Impaired erythrocyte deformability precedes vascular changes in experimental diabetes mellitus. Horm Metab Res. 2004;36:142–7. Shin S, Ku YH, Suh JS, Singh M. Rheological characteristics of erythrocytes incubated in glucose media. Clin Hemorheol Microcirc. 2008;38:153–61. Shin S, Ku YH, Ho JX, Kim YK, Suh JS, Singh M. Progressive impairment of erythrocyte deformability as indicator of microangiopathy in type 2 diabetes mellitus. Clin Hemorheol Microcirc. 2007;36:253–61. Linderkamp O, Ruef P, Zilow EP, Hoffmann GF. Impaired deformability of erythrocytes and neutrophils in children with newly diagnosed insulin-dependent diabetes mellitus. Diabetologia. 1999;42:865–9. Forst T, Weber MM, Löbig M, Lehmann U, Müller J, Hohberg C, et al. Pioglitazone in addition to metformin improves erythrocyte deformability in patients with type 2 diabetes mellitus. Clin Sci (Lond). 2010;119:345–51. Satoh M, Imaizumi K, Bessho T, Shiga T. Increased erythrocyte aggregation in diabetes mellitus and its relationship to glycosylated haemoglobin and retinopathy. Diabetologia. 1984;27:517–21. Elishkevitz K, Fusman R, Koffler M, Shapira I, Zeltser D, Avitzour D, et al. Rheological determinants of red blood cell aggregation in diabetic patients in relation to their metabolic control. Diabet Med. 2002;19:152–6. Uyesaka N, Hasegawa S, Ishioka N, Ishioka R, Shio H, Schechter AN. Effects of superoxide anions on red cell deformability and membrane proteins. Biorheology. 1992;29:217–29. Iwata H, Ukeda H, Maruyama T, Fujino T, Sawamura M. Effect of carbonyl compounds on red blood cells deformability. Biochem Biophys Res Commun. 2004;321:700–6. Okamoto K, Maruyama T, Kaji Y, Harada M, Mawatari S, Fujino T, et al. Verapamil prevents impairment in filterability of human erythrocytes exposed to oxidative stress. Jpn J Physiol. 2004;54:39–46. Mawatari S, Murakami K. Effects of ascorbate on membrane phospholipids and tocopherols of intact erythrocytes during peroxidation by t-butylhydroperoxide: comparison with effects of dithiothreitol. Lipids. 2001;36:57–65. Ahmed FN, Naqvi FN, Shafiq F. Lipid peroxidation and serum antioxidant enzymes in patients with type 2 diabetes mellitus. Ann NY Acad Sci. 2006;1084:481–9. Hansel B, Giral P, Nobecourt E, Chantepie S, Bruckert E, Chapman MJ, et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab. 2004;89:4963–71. Ford ES, Mokdad AH, Giles WH, Brown DW. The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutritional Examination Survey. Diabetes. 2003;52:2346–52. Anichkov DA, Maksina AG, Shostak NA. Relationships between erythrocyte membrane properties and components of metabolic syndrome in women. Med Sci Monit. 2005;11:CR203–10. Solá E, Vayá A, Santaolaria ML, Hernández-Mijares A, Réganon E, Vila V, et al. Erythrocyte deformability in obesity measured by ektacytometric techniques. Clin Hemorheol Microcirc. 2007;37:219–27. Kraemer-Aguiar LG, Laflor CM, Bouskela E. Skin microcirculatory dysfunction is already present in normoglycemic subjects with metabolic syndrome. Metabolism. 2008;57:1740–6. Grassi G, Seravalle G, Brambilla G, Facchetti R, Bolla G, Mozzi E, Mancia G. Impact of the metabolic syndrome on subcutaneous microcirculation in obese patients. J Hypertens. 2010;28:1708–14.