The Number and Potency of Endothelial Progenitor Cells in Type 2 Diabetes Mellitus Patients
Abstract
BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a metabolic disease, due to the disorder of insulin function, insulin secretion, or both. Long-term hyperglycemia conditions promote endothelial dysfunction precedes to the development of multiple organ dysfunctions. Endothelial progenitor cells (EPCs) and hematopoietic stem cell (HSCs) are the key cellular effectors of postnatal neovascularization and play central role in endothelial dysfunction. However, in T2DM condition, the number of apoptotic HSCs increase, it may cause the reduction in potency and number of EPCs. In diabetes, the circulating EPCs number decrease and their functionality is impaired, but mechanism underlie of this impairement is unknown. The purpose of this study was to examine the relationship duration diabetes with the number and potency of EPC cells in T2DM patients controlled and poorly controlled.
METHODS: Thirty-eight T2DM male patients were classified into two group based on Indonesian Society of Endocrinology/Perkumpulan Endokrinologi Indonesia (PERKENI) criteria on T2DM. The first group was a controlled glycemic condition group (hemoglobin A1c (HbA1C) <7.0%) and the second group was a poorly controlled glycemic condition group (HbA1C >7.0%). Cluster of differentiation (CD)34+ and CD133+ expressions were used as specific marker for EPC, while quantified bright aldehyde dehydrogenase (ALDHbr) assay was used to represented the potency of EPCs.
RESULTS: This study showed that in poorly controlled T2DM group the number of EPCs was lower by 24.80% (p<0.05) compared to the T2DM controlled group. Similarly, the expression of ALDHbr was lower by 43.07% (p<0.05) in poorly controlled group.
CONCLUSION: There was a decrease in the number and potency of EPCs in poorly controlled T2DM patients compared to the controlled T2DM patients. There was also a strong negative correlation between the duration of diabetes and number of EPCs.
KEYWORDS: ALDHbr, endothelial progenitor cells, type 2 diabetes mellitus
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American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010; 34 (Suppl 1): S62-9, CrossRef.
Indonesian Society of Endocrinology/Perkumpulan Endokrinologi Indonesia (PERKENI). Konsensus Pengelolaan dan pencegahan Diabetes melitus di Indonesia. Jakarta: PERKENI; 2015, article.
Mapanga R, Essop M. Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways. Am J Physiol Heart Circ Physiol. 2016; 310: H153-73, CrossRef.
Fadini G, Sartore S, Agostini C, Avogaro A. Significance of endothelial progenitor cells in subjects with diabetes. Diabetes Care. 2007; 30: 1305-13, CrossRef.
Yoder M. Human endothelial progenitor cells. Cold Spring Harb Perspect Med. 2011; 2: a006692, CrossRef.
Chirayath H. An overview of endothelial dysfunction in diabetes. Vascul Dis Ther. 2016; 1: 1-3, CrossRef.
Issan Y, Hochhauser E, Kornowski R, Leshem-Lev D, Lev E, Sharoni R, et al. Endothelial progenitor cell function inversely correlates with long-term glucose control in diabetic patients: association with the attenuation of the heme oxygenase-adiponectin axis. Can J Cardiol. 2012; 28: 728-36, CrossRef.
Rajasekar P, O’Neill C, Eeles L, Stitt A, Medina R. Epigenetic changes in endothelial progenitors as a possible cellular basis for glycemic memory in diabetic vascular complications. J Diabetes Res. 2015; 2015: 436879, CrossRef.
Churdchomjan W, Kheolamai P, Manochantr S, Tapanadechopone P, Tantrawatpan C, U-pratya Y, et al. Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control. BMC Endocr Disord. 2010; 10: 5, CrossRef.
Szpera-Goździewicz A, Majcherek M, Boruczkowski M, Goździewicz T, Dworacki G, Wicherek L, et al. Circulating endothelial cells, circulating endothelial progenitor cells, and von Willebrand factor in pregnancies complicated by hypertensive disorders. Am Reprod Immunol. 2017; 77: e12625, CrossRef.
Balber AE. Aldehyde dehydrogenase bright stem and progenitor cell populations from normal tissues: characteristics, activities, and emerging uses in regenerative medicine. Stem Cells. 2011; 29: 570-5, CrossRef.
Imanishi T, Tsujioka H, Akasaka T. Endothelial progenitor cells dysfunction and senescence: contribution to oxidative stress. Curr Cardiol Rev. 2008; 4: 275-86, CrossRef.
Shao L, Li H, Pazhanisamy S, Meng A, Wang Y, Zhou D. Reactive oxygen species and hematopoietic stem cell senescence. Int J Hematol. 2011; 94: 24-32, CrossRef.
Chen F, Liu Y, Wong N, Xiao J, So K. Oxidative stress in stem cell aging. Cell Transplant. 2017; 26: 1483-95, CrossRef.
Alison M, Guppy N, Lim S, Nicholson L. Finding cancer stem cells: are aldehyde dehydrogenases fit for purpose?. J Pathol. 2010; 222: 335-44, CrossRef.
Shoulars K, Noldner P, Troy J, Cheatham L, Parrish A, Page K, et al. Development and validation of a rapid, aldehyde dehydrogenase bright-based cord blood potency assay. Blood. 2016; 127: 2346-54, CrossRef.
Prieto-Vila M, Takahashi R, Usuba W, Kohama I, Ochiya T. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci. 2017; 18: 2574, CrossRef.
White H, Smith L, Gentry T, Balber AE. Mechanisms of action of human aldehyde dehydrogenase bright cells in therapy of cardiovascular diseases: expression analysis of angiogenic factors and aldehyde dehydrogenase isozymes. J Stem Cell Res Ther. 2011; S1: 1-9, CrossRef.
Makino H, Miyamoto Y, Kikuchi-Taura A, Soma T, Taguchi A, Kishimoto I. Decreased levels of circulating CD34+ cells are associated with coronary heart disease in Japanese patients with type 2 diabetes. J Diabetes Invest. 2014; 6: 473-8, CrossRef.
Nowak W, Borys S, Kusińska K, Bukowska-Strakova K, Witek P, Koblik T, et al. Number of circulating pro-angiogenic cells, growth factor and anti-oxidative gene profiles might be altered in type 2 diabetes with and without diabetic foot syndrome. J Diabetes Invest. 2013; 5: 99-107, CrossRef.
Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res. 2004; 95: 343-53, PMID.
DOI: https://doi.org/10.18585/inabj.v11i2.576
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The Prodia Education and Research Institute
