Impaired deformability of erythrocytes in diabetic rat and human: investigation by the nickel-mesh-filtration technique
- 57 Downloads
- 4 Citations
Abstract
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.
Keywords
Deformability Diabetic patient Diabetic rat Erythrocytes Filtration Microcirculation Nickel-meshNotes
Acknowledgments
The authors would like to thank staff of the Institute of Rheological Function of Foods Co. Ltd. (Hisayama, Fukuoka) for technical assistance and staff of affiliated hospitals involved in this project for clinical assistance. We lost our collaborator, Dr Nobuhiro Uyesaka (Department of Physiology, Nippon Medical University) during the preparation of this manuscript, and dedicate this work to honor his memory.
Conflicts of interest
The authors declare that there are no conflicts of interest in relation to this manuscript.
References
- 1.Caimi G, Presti RL. Techniques to evaluate erythrocyte deformability in diabetes mellitus. Acta Diabetol. 2004;41:99–103.CrossRefGoogle Scholar
- 2.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.CrossRefGoogle Scholar
- 3.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.Google Scholar
- 4.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.Google Scholar
- 5.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.CrossRefGoogle Scholar
- 6.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.Google Scholar
- 7.Arai K, Iino M, Shio H, Uyesaka N. Further investigations of red cell deformability with nickel mesh. Biorheology. 1990;27:47–65.Google Scholar
- 8.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.Google Scholar
- 9.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.Google Scholar
- 10.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.CrossRefGoogle Scholar
- 11.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.CrossRefGoogle Scholar
- 12.Ramesh B, Pugalendi KV. Influence of umbelliferone on membrane-bound ATPases in streptozotocin-induced diabetic rats. Pharmacol Rep. 2007;59:339–48.Google Scholar
- 13.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.CrossRefGoogle Scholar
- 14.Shin S, Ku YH, Suh JS, Singh M. Rheological characteristics of erythrocytes incubated in glucose media. Clin Hemorheol Microcirc. 2008;38:153–61.Google Scholar
- 15.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.Google Scholar
- 16.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.CrossRefGoogle Scholar
- 17.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.CrossRefGoogle Scholar
- 18.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.CrossRefGoogle Scholar
- 19.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.CrossRefGoogle Scholar
- 20.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.Google Scholar
- 21.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.CrossRefGoogle Scholar
- 22.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.CrossRefGoogle Scholar
- 23.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.CrossRefGoogle Scholar
- 24.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.CrossRefADSGoogle Scholar
- 25.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.CrossRefGoogle Scholar
- 26.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.CrossRefGoogle Scholar
- 27.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.Google Scholar
- 28.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.Google Scholar
- 29.Kraemer-Aguiar LG, Laflor CM, Bouskela E. Skin microcirculatory dysfunction is already present in normoglycemic subjects with metabolic syndrome. Metabolism. 2008;57:1740–6.CrossRefGoogle Scholar
- 30.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.CrossRefGoogle Scholar