The authors declare that there is no competing interest associated with this manuscript.
CTZ coordinated analyses, interpreted results and wrote the manuscript. MW performed statistical analyses and revised the manuscript. CWS advised and supervised statistical analyses and revised the manuscript. YLH and TW were involved in the conception and design of the study, interpretation of the data, ongoing support and advice to the first author. KHY contributed to study design, data interpretation and manuscript revision. HFT designed and led the project and revised the manuscript. All authors have approved the final version of the manuscript.
Endothelial progenitor cells (EPCs) are responsible for angiogenesis and maintenance of microvascular integrity, the number of EPCs is correlated with oxidative stress. Their relation to myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) is nonetheless unknown.
Eighty-seven patients with T2DM and no history of coronary artery disease were recruited. Transthoracic echocardiography and detailed evaluation of left ventricular (LV) systolic function by 2-dimensional (2D) speckle tracking derived strain analysis in 3 orthogonal directions was performed. Four subpopulations of EPCs, including CD34+, CD133+, CD34+/kinase insert domain-containing receptor (KDR) + and CD133+/KDR + EPCs, were measured by flow cytometry. Oxidative stress was assessed by superoxide dismutase (SOD).
The mean age of the patients was 62 ± 9 years and 39.6% were male. Those with an impaired longitudinal strain had a lower number of CD34+ EPCs (2.82 ± 1.87% vs. 3.74 ± 2.12%, P < 0.05) than those with preserved longitudinal strain. When compared with those with preserved circumferential strain, patients with an impaired circumferential strain had a lower number of CD34+ EPCs (2.63 ± 1.80% vs. 3.87 ± 2.10%, P < 0.01) and SOD level (0.13 ± 0.06U/ml vs. 0.20 ± 0.08U/ml, P < 0.01). Patients with an impaired radial strain nonetheless had a lower number of CD34+ EPCs (2.62 ± 2.08% vs. 3.69 ± 1.99%, P < 0.05). Multivariate analysis demonstrated that only impaired global circumferential strain remained significantly associated with CD34 + EPCs and SOD.
LV global circumferential strain was independently associated with number of CD34+ EPCs and SOD. These findings suggest that myocardial dysfunction in patients with T2DM is related to depletion of EPCs and increased oxidative stress.
Aksakal E, Akaras N, Kurt M, Tanboga IH, Halici Z, Odabasoglu F, Bakirci EM, Unal B: The role of oxidative stress in diabetic cardiomyopathy: an experimental study. Eur Rev Med Pharmacol Sci. 2011, 15: 1241-1246. PubMed
Yoon YS, Uchida S, Masuo O, Cejna M, Park JS, Gwon HC, Kirchmair R, Bahlman F, Walter D, Curry C, et al: Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy: restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor. Circulation. 2005, 111 (16): 2073-2085. 10.1161/01.CIR.0000162472.52990.36. CrossRefPubMed
Miki T, Yuda S, Kouzu H, Miura T: Diabetic cardiomyopathy: pathophysiology and clinical features. Hear Fail Rev. 2012, [epud ahead of print]
Fadini GP, Mancuso P, Bertolini F, de Kreutzenberg S, Avogaro A: Amelioration of glucose control mobilizes circulating pericyte progenitor cells in type 2 diabetic patients with microangiopathy. Exp Diabetes Res. 2012, Epud ahead of print
Cheng Y, Guo S, Liu G, Feng Y, Yan B, Yu J, Feng K, Li Z: Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats. Int J Mol Med. 2012, Epud ahead of print
Ernande L, Bergerot C, Rietzschel ER, De Buyzere ML, Thibault H, Pignonblanc PG, Croisille P, Ovize M, Groisne L, Moulin P, et al: Diastolic dysfunction in patients with type 2 diabetes mellitus: is it really the first marker of diabetic cardiomyopathy?. J Am Soc Echocardiogr. 2011, 24 (11): 1268-1275. 10.1016/j.echo.2011.07.017. e1261 CrossRefPubMed
Ng AC, Delgado V, Bertini M, van der Meer RW, Rijzewijk LJ, Shanks M, Nucifora G, Smit JW, Diamant M, Romijn JA, et al: Findings from left ventricular strain and strain rate imaging in asymptomatic patients with type 2 diabetes mellitus. Am J Cardiol. 2009, 104: 1398-1401. 10.1016/j.amjcard.2009.06.063. CrossRefPubMed
Lau KK, Chan YH, Yiu KH, Li SW, Tam S, Lau CP, Kwong YL, Tse HF: Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension. J Hum Hypertens. 2007, 21 (6): 445-451. PubMed
Luk TH, Dai YL, Siu CW, Yiu KH, Chan HT, Fong DY, Lee SW, Li SW, Tam S, Lau CP, et al: Habitual physical activity is associated with endothelial function and endothelial progenitor cells in patients with stable coronary artery disease. Eur J Cardiovasc Prev Rehabil. 2009, 16 (4): 464-471. 10.1097/HJR.0b013e32832b38be. CrossRefPubMed
Dai YL, Luk TH, Yiu KH, Wang M, Yip PM, Lee SW, Li SW, Tam S, Fong B, Lau CP, et al: Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial. Atherosclerosis. 2011, 216: 395-401. 10.1016/j.atherosclerosis.2011.02.013. CrossRefPubMed
Wong CY, Qiuwaxi J, Chen H, Li SW, Chan HT, Tam S, Shu XO, Lau CP, Kwong YL, Tse HF: Daily intake of thiamine correlates with the circulating level of endothelial progenitor cells and the endothelial function in patients with type II diabetes. Mol Nutr Food Res. 2008, 52 (12): 1421-1427. 10.1002/mnfr.200800056. CrossRefPubMed
Delgado V, Ypenburg C, van Bommel RJ, Tops LF, Mollema SA, Marsan NA, Bleeker GB, Schalij MJ, Bax JJ: Assessment of left ventricular dyssynchrony by speckle tracking strain imaging comparison between longitudinal, circumferential, and radial strain in cardiac resynchronization therapy. J Am Coll Cardiol. 2008, 51 (20): 1944-1952. 10.1016/j.jacc.2008.02.040. CrossRefPubMed
Takigiku K, Takeuchi M, Izumi C, Yuda S, Sakata K, Ohte N, Tanabe K, Nakatani S, on behalf of the JUSTICE investigators: Normal Range of Left Ventricular 2-Dimensional Strain. Circ J. 2012, Epud ahead of print
Ng AC, Delgado V, Bertini M, van der Meer RW, Rijzewijk LJ, Hooi Ewe S, Siebelink HM, Smit JW, Diamant M, Romijn JA, et al: Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus. Circulation. 2010, 122: 2538-2544. 10.1161/CIRCULATIONAHA.110.955542. CrossRefPubMed
Jellis C, Wright J, Kennedy D, Sacre J, Jenkins C, Haluska B, Martin J, Fenwick J, Marwick TH: Association of imaging markers of myocardial fibrosis with metabolic and functional disturbances in early diabetic cardiomyopathy. Circ Cardiovasc Imaging. 2011, 6: 693-702. CrossRef
Andersson C, Gislason GH, Weeke P, Hoffmann S, Hansen PR, Torp-Pedersen C, Søgaard P: Diabetes is associated with impaired myocardial performance in patients without significant coronary artery disease. Cardiovasc Diabetol. 2010, 18: 3. CrossRef
Kawaguchi M, Techigawara M, Ishihata T, Asakura T, Saito F, Maehara K, Maruyama Y: A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension. Hear Vessel. 1997, 12: 267-274. 10.1007/BF02766802. CrossRef
De Lorenzo A, Lima RS, Siqueira-Filho AG, Pantoja MR: Prevalence and prognostic value of perfusion defects detected by stress technetium-99 m sestamibi myocardial perfusion single-photon emission computed tomography in asymptomatic patients with diabetes mellitus and no known coronary artery disease. Am J Cardiol. 2002, 90: 827-832. 10.1016/S0002-9149(02)02702-9. CrossRefPubMed
Palombo C, Kozakova M, Morizzo C, Gnesi L, Barsotti MC, Spontoni P, Massart F, Salvi P, Balbarini A, Saggese G, et al: Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated type 1 diabetes. Cardiovasc Diabetol. 2011, 10: 88-10.1186/1475-2840-10-88. PubMedCentralCrossRefPubMed
Yiu YF, Chan YH, Yiu KH, Siu CW, Li SW, Wong LY, Lee SW, Tam S, Wong EW, Cheung BM, et al: Vitamin D deficiency is associated with depletion of circulating endothelial progenitor cells and endothelial dysfunction in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011, 96: E830-E835. 10.1210/jc.2010-2212. CrossRefPubMed
Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, de Kreutzenberg SV, Tiengo A, Agostini C, et al: Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005, 45: 1449-1457. 10.1016/j.jacc.2004.11.067. CrossRefPubMed
Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, et al: Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006, 26 (9): 2140-2146. 10.1161/01.ATV.0000237750.44469.88. CrossRefPubMed
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G: Circulating endothelial progenitor cells and cardiovascular outcomes. N Eng J Med. 2005, 353: 999-1007. 10.1056/NEJMoa043814. CrossRef
Huynh K, Kiriazis H, Du XJ, Love JE, Jandeleit-Dahm KA, Forbes JM, McMullen JR, Ritchie RH: Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes. Diabetologia. 2012, 55: 1544-1553. 10.1007/s00125-012-2495-3. CrossRefPubMed
Khong FL, Zhang Y, Edgley AJ, Qi W, Connelly KA, Woodman OL, Krum H, Kelly DJ: 3′,4′-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats. PLoS One. 2011, 6: e22777-10.1371/journal.pone.0022777. PubMedCentralCrossRefPubMed
- Myocardial dysfunction in patients with type 2 diabetes mellitus: role of endothelial progenitor cells and oxidative stress
Chun Ting Zhao
Chung Wah Siu
Ying Long Hou
Hung Fat Tse
Kai Hang Yiu
- BioMed Central
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