Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2014

Open Access 01-12-2014 | Original investigation

Exercise increases serum endostatin levels in female and male patients with diabetes and controls

Authors: Michael Sponder, Daniela Dangl, Stephanie Kampf, Monika Fritzer-Szekeres, Jeanette Strametz-Juranek

Published in: Cardiovascular Diabetology | Issue 1/2014

Login to get access

Abstract

Background

Type 2 diabetes mellitus (T2DM) is often associated with atherosclerotic changes in coronary vessels, most notably plaques. The angiostatic parameter endostatin is able to inhibit angiogenesis in tissue as well as in plaques and therefore plays an important role in physiological and pathological neovascularisation. The aim of the present study was to investigate sex-specific differences and the influence of exercise on circulating endostatin levels in patients suffering from diabetes, and control subjects.

Methods

In total, 42 T2DM-patients and 45 control subjects were investigated. They underwent a graded physical stress test (ergometry). Serum endostatin levels were measured in venous blood at rest and directly after reaching maximum workload.

Results

Females showed significantly higher endostatin levels at baseline measurements compared to men, independently of their underlying disease. In both female and male T2DM-patients endostatin levels were significantly lower compared to controls. Both groups and sexes showed a significant increase of endostatin after physical stress, whereas the extent of endostatin-increase was between 10.59-15.05%.

Conclusion

Middle-aged healthy female individuals as well as female T2DM-patients showed higher circulating serum endostatin levels compared to males, suggesting a hormonal influence on baseline circulating endostatin amounts. Exercise-induced increase in endostatin is also observable in patients suffering from T2DM. Concerning vascularisation, lower endostatin levels in T2DM might be advantageous. Concerning plaque stability, lower levels might be prejudicial.

Trial registration

Literature
1.
go back to reference Mosca L, Grundy SM, Judelson D, King K, Limacher M, Oparil S, Pasternak R, Pearson TA, Redberg RF, Smith SC, et al: Guide to preventive cardiology for women. AHA/ACC scientific statement consensus panel statement. Circulation. 1999, 99: 2480-2484. 10.1161/01.CIR.99.18.2480.CrossRefPubMed Mosca L, Grundy SM, Judelson D, King K, Limacher M, Oparil S, Pasternak R, Pearson TA, Redberg RF, Smith SC, et al: Guide to preventive cardiology for women. AHA/ACC scientific statement consensus panel statement. Circulation. 1999, 99: 2480-2484. 10.1161/01.CIR.99.18.2480.CrossRefPubMed
2.
go back to reference Mascarenhas-Melo F, Marado D, Palavra F, Sereno J, Coelho A, Pinto R, Teixeira-Lemos E, Teixeira F, Reis F: Diabetes abrogates sex differences and aggravates cardiometabolic risk in postmenopausal women. Cardiovasc Diabetol. 2013, 12: 61-10.1186/1475-2840-12-61.PubMedCentralCrossRefPubMed Mascarenhas-Melo F, Marado D, Palavra F, Sereno J, Coelho A, Pinto R, Teixeira-Lemos E, Teixeira F, Reis F: Diabetes abrogates sex differences and aggravates cardiometabolic risk in postmenopausal women. Cardiovasc Diabetol. 2013, 12: 61-10.1186/1475-2840-12-61.PubMedCentralCrossRefPubMed
3.
go back to reference Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pina IL, Roger VL, Shaw LJ, et al: Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the american heart association. Circulation. 2011, 123: 1243-1262. 10.1161/CIR.0b013e31820faaf8.PubMedCentralCrossRefPubMed Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pina IL, Roger VL, Shaw LJ, et al: Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the american heart association. Circulation. 2011, 123: 1243-1262. 10.1161/CIR.0b013e31820faaf8.PubMedCentralCrossRefPubMed
4.
go back to reference Dong S, Cole GJ, Halfter W: Expression of collagen XVIII and localization of its glycosaminoglycan attachment sites. J Biol Chem. 2003, 278: 1700-1707. 10.1074/jbc.M209276200.CrossRefPubMed Dong S, Cole GJ, Halfter W: Expression of collagen XVIII and localization of its glycosaminoglycan attachment sites. J Biol Chem. 2003, 278: 1700-1707. 10.1074/jbc.M209276200.CrossRefPubMed
5.
go back to reference Rehn M, Pihlajaniemi T: Alpha 1(XVIII), a collagen chain with frequent interruptions in the collagenous sequence, a distinct tissue distribution, and homology with type XV collagen. Proc Natl Acad Sci USA. 1994, 91: 4234-4238. 10.1073/pnas.91.10.4234.PubMedCentralCrossRefPubMed Rehn M, Pihlajaniemi T: Alpha 1(XVIII), a collagen chain with frequent interruptions in the collagenous sequence, a distinct tissue distribution, and homology with type XV collagen. Proc Natl Acad Sci USA. 1994, 91: 4234-4238. 10.1073/pnas.91.10.4234.PubMedCentralCrossRefPubMed
6.
go back to reference Oh SP, Warman ML, Seldin MF, Cheng SD, Knoll JH, Timmons S, Olsen BR: Cloning of cDNA and genomic DNA encoding human type XVIII collagen and localization of the alpha 1(XVIII) collagen gene to mouse chromosome 10 and human chromosome 21. Genomics. 1994, 19: 494-499. 10.1006/geno.1994.1098.CrossRefPubMed Oh SP, Warman ML, Seldin MF, Cheng SD, Knoll JH, Timmons S, Olsen BR: Cloning of cDNA and genomic DNA encoding human type XVIII collagen and localization of the alpha 1(XVIII) collagen gene to mouse chromosome 10 and human chromosome 21. Genomics. 1994, 19: 494-499. 10.1006/geno.1994.1098.CrossRefPubMed
7.
go back to reference O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997, 88: 277-285. 10.1016/S0092-8674(00)81848-6.CrossRefPubMed O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997, 88: 277-285. 10.1016/S0092-8674(00)81848-6.CrossRefPubMed
8.
go back to reference Yamaguchi N, Anand-Apte B, Lee M, Sasaki T, Fukai N, Shapiro R, Que I, Lowik C, Timpl R, Olsen BR: Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. EMBO J. 1999, 18: 4414-4423. 10.1093/emboj/18.16.4414.PubMedCentralCrossRefPubMed Yamaguchi N, Anand-Apte B, Lee M, Sasaki T, Fukai N, Shapiro R, Que I, Lowik C, Timpl R, Olsen BR: Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. EMBO J. 1999, 18: 4414-4423. 10.1093/emboj/18.16.4414.PubMedCentralCrossRefPubMed
9.
go back to reference Rehn M, Veikkola T, Kukk-Valdre E, Nakamura H, Ilmonen M, Lombardo C, Pihlajaniemi T, Alitalo K, Vuori K: Interaction of endostatin with integrins implicated in angiogenesis. Proc Natl Acad Sci U S A. 2001, 98: 1024-1029. 10.1073/pnas.98.3.1024.PubMedCentralCrossRefPubMed Rehn M, Veikkola T, Kukk-Valdre E, Nakamura H, Ilmonen M, Lombardo C, Pihlajaniemi T, Alitalo K, Vuori K: Interaction of endostatin with integrins implicated in angiogenesis. Proc Natl Acad Sci U S A. 2001, 98: 1024-1029. 10.1073/pnas.98.3.1024.PubMedCentralCrossRefPubMed
10.
go back to reference Cho H, Kim WJ, Lee YM, Kim YM, Kwon YG, Park YS, Choi EY, Kim KW: N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent. Oncol Rep. 2004, 11: 191-195.PubMed Cho H, Kim WJ, Lee YM, Kim YM, Kwon YG, Park YS, Choi EY, Kim KW: N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent. Oncol Rep. 2004, 11: 191-195.PubMed
11.
go back to reference Booth FW, Gordon SE, Carlson CJ, Hamilton MT: Waging war on modern chronic diseases: primary prevention through exercise biology. J Appl Physiol. 2000, 88: 774-787.PubMed Booth FW, Gordon SE, Carlson CJ, Hamilton MT: Waging war on modern chronic diseases: primary prevention through exercise biology. J Appl Physiol. 2000, 88: 774-787.PubMed
12.
go back to reference Francis K: The burden of physical inactivity & cardiovascular heart disease. Compr Ther. 1998, 24: 87-92.PubMed Francis K: The burden of physical inactivity & cardiovascular heart disease. Compr Ther. 1998, 24: 87-92.PubMed
13.
go back to reference Manson JE, Hu FB, Rich-Edwards JW, Colditz GA, Stampfer MJ, Willett WC, Speizer FE, Hennekens CH: A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women. N Engl J Med. 1999, 341: 650-658. 10.1056/NEJM199908263410904.CrossRefPubMed Manson JE, Hu FB, Rich-Edwards JW, Colditz GA, Stampfer MJ, Willett WC, Speizer FE, Hennekens CH: A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women. N Engl J Med. 1999, 341: 650-658. 10.1056/NEJM199908263410904.CrossRefPubMed
14.
go back to reference Sacco RL, Benjamin EJ, Broderick JP, Dyken M, Easton JD, Feinberg WM, Goldstein LB, Gorelick PB, Howard G, Kittner SJ, et al: American Heart Association Prevention Conference. IV. Prevention and rehabilitation of stroke. Risk factors. Stroke. 1997, 28: 1507-1517. 10.1161/01.STR.28.7.1507.CrossRefPubMed Sacco RL, Benjamin EJ, Broderick JP, Dyken M, Easton JD, Feinberg WM, Goldstein LB, Gorelick PB, Howard G, Kittner SJ, et al: American Heart Association Prevention Conference. IV. Prevention and rehabilitation of stroke. Risk factors. Stroke. 1997, 28: 1507-1517. 10.1161/01.STR.28.7.1507.CrossRefPubMed
15.
go back to reference Jensen L, Schjerling P, Hellsten Y: Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells. Angiogenesis. 2004, 7: 255-267. 10.1007/s10456-004-4184-4.CrossRefPubMed Jensen L, Schjerling P, Hellsten Y: Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells. Angiogenesis. 2004, 7: 255-267. 10.1007/s10456-004-4184-4.CrossRefPubMed
16.
go back to reference Gu JW, Gadonski G, Wang J, Makey I, Adair TH: Exercise increases endostatin in circulation of healthy volunteers. BMC Physiol. 2004, 4: 2-10.1186/1472-6793-4-2.PubMedCentralCrossRefPubMed Gu JW, Gadonski G, Wang J, Makey I, Adair TH: Exercise increases endostatin in circulation of healthy volunteers. BMC Physiol. 2004, 4: 2-10.1186/1472-6793-4-2.PubMedCentralCrossRefPubMed
17.
go back to reference Rullman E, Rundqvist H, Wagsater D, Fischer H, Eriksson P, Sundberg CJ, Jansson E, Gustafsson T: A single bout of exercise activates matrix metalloproteinase in human skeletal muscle. J Appl Physiol. 2007, 102: 2346-2351. 10.1152/japplphysiol.00822.2006.CrossRefPubMed Rullman E, Rundqvist H, Wagsater D, Fischer H, Eriksson P, Sundberg CJ, Jansson E, Gustafsson T: A single bout of exercise activates matrix metalloproteinase in human skeletal muscle. J Appl Physiol. 2007, 102: 2346-2351. 10.1152/japplphysiol.00822.2006.CrossRefPubMed
18.
go back to reference Suhr F, Brixius K, de Marees M, Bolck B, Kleinoder H, Achtzehn S, Bloch W, Mester J: Effects of short-term vibration and hypoxia during high-intensity cycling exercise on circulating levels of angiogenic regulators in humans. J Appl Physiol. 2007, 103: 474-483. 10.1152/japplphysiol.01160.2006.CrossRefPubMed Suhr F, Brixius K, de Marees M, Bolck B, Kleinoder H, Achtzehn S, Bloch W, Mester J: Effects of short-term vibration and hypoxia during high-intensity cycling exercise on circulating levels of angiogenic regulators in humans. J Appl Physiol. 2007, 103: 474-483. 10.1152/japplphysiol.01160.2006.CrossRefPubMed
19.
go back to reference Gu JW, Shparago M, Tan W, Bailey AP: Tissue endostatin correlates inversely with capillary network in rat heart and skeletal muscles. Angiogenesis. 2006, 9: 93-99. 10.1007/s10456-006-9035-z.CrossRefPubMed Gu JW, Shparago M, Tan W, Bailey AP: Tissue endostatin correlates inversely with capillary network in rat heart and skeletal muscles. Angiogenesis. 2006, 9: 93-99. 10.1007/s10456-006-9035-z.CrossRefPubMed
20.
go back to reference Suhr F, Rosenwick C, Vassiliadis A, Bloch W, Brixius K: Regulation of extracellular matrix compounds involved in angiogenic processes in short- and long-track elite runners. Scand J Med Sci Sports. 2010, 20: 441-448.CrossRefPubMed Suhr F, Rosenwick C, Vassiliadis A, Bloch W, Brixius K: Regulation of extracellular matrix compounds involved in angiogenic processes in short- and long-track elite runners. Scand J Med Sci Sports. 2010, 20: 441-448.CrossRefPubMed
21.
go back to reference Trappe HJ, Lollgen H: Guidelines for ergometry. German Society of Cardiology–Heart and Cardiovascular Research. Z Kardiol. 2000, 89: 821-831.CrossRefPubMed Trappe HJ, Lollgen H: Guidelines for ergometry. German Society of Cardiology–Heart and Cardiovascular Research. Z Kardiol. 2000, 89: 821-831.CrossRefPubMed
22.
go back to reference Gui C, Li SK, Nong QL, Du F, Zhu LG, Zeng ZY: Changes of serum angiogenic factors concentrations in patients with diabetes and unstable angina pectoris. Cardiovasc Diabetol. 2013, 12: 34-10.1186/1475-2840-12-34.PubMedCentralCrossRefPubMed Gui C, Li SK, Nong QL, Du F, Zhu LG, Zeng ZY: Changes of serum angiogenic factors concentrations in patients with diabetes and unstable angina pectoris. Cardiovasc Diabetol. 2013, 12: 34-10.1186/1475-2840-12-34.PubMedCentralCrossRefPubMed
23.
go back to reference Mieno S, Boodhwani M, Robich MP, Clements RT, Sodha NR, Sellke FW: Effects of diabetes mellitus on VEGF-induced proliferation response in bone marrow derived endothelial progenitor cells. J Card Surg. 2010, 25: 618-625. 10.1111/j.1540-8191.2010.01086.x.PubMedCentralCrossRefPubMed Mieno S, Boodhwani M, Robich MP, Clements RT, Sodha NR, Sellke FW: Effects of diabetes mellitus on VEGF-induced proliferation response in bone marrow derived endothelial progenitor cells. J Card Surg. 2010, 25: 618-625. 10.1111/j.1540-8191.2010.01086.x.PubMedCentralCrossRefPubMed
24.
go back to reference Boodhwani M, Sodha NR, Mieno S, Xu SH, Feng J, Ramlawi B, Clements RT, Sellke FW: Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes. Circulation. 2007, 116: I31-37.PubMedCentralCrossRefPubMed Boodhwani M, Sodha NR, Mieno S, Xu SH, Feng J, Ramlawi B, Clements RT, Sellke FW: Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes. Circulation. 2007, 116: I31-37.PubMedCentralCrossRefPubMed
25.
go back to reference Bruserud O, Grovan F, Lindas R, Blymke Moinichen C, Osterhus KK: Serum levels of angioregulatory mediators in healthy individuals depend on age and physical activity: studies of angiogenin, basic fibroblast growth factor, leptin and endostatin. Scand J Clin Lab Invest. 2005, 65: 505-511. 10.1080/00365510500209306.CrossRefPubMed Bruserud O, Grovan F, Lindas R, Blymke Moinichen C, Osterhus KK: Serum levels of angioregulatory mediators in healthy individuals depend on age and physical activity: studies of angiogenin, basic fibroblast growth factor, leptin and endostatin. Scand J Clin Lab Invest. 2005, 65: 505-511. 10.1080/00365510500209306.CrossRefPubMed
26.
go back to reference Brixius K, Schoenberger S, Ladage D, Knigge H, Falkowski G, Hellmich M, Graf C, Latsch J, Montie GL, Prede GL, Bloch W: Long-term endurance exercise decreases antiangiogenic endostatin signalling in overweight men aged 50–60 years. Br J Sports Med. 2008, 42: 126-129. discussion 129CrossRefPubMed Brixius K, Schoenberger S, Ladage D, Knigge H, Falkowski G, Hellmich M, Graf C, Latsch J, Montie GL, Prede GL, Bloch W: Long-term endurance exercise decreases antiangiogenic endostatin signalling in overweight men aged 50–60 years. Br J Sports Med. 2008, 42: 126-129. discussion 129CrossRefPubMed
27.
go back to reference Makey KL, Patterson SG, Robinson J, Loftin M, Waddell DE, Miele L, Chinchar E, Huang M, Smith AD, Weber M, Gu JW: Increased plasma levels of soluble vascular endothelial growth factor receptor 1 (sFlt-1) in women by moderate exercise and increased plasma levels of vascular endothelial growth factor in overweight/obese women. Eur J Cancer Prev. 2012, 22: 83-89.CrossRef Makey KL, Patterson SG, Robinson J, Loftin M, Waddell DE, Miele L, Chinchar E, Huang M, Smith AD, Weber M, Gu JW: Increased plasma levels of soluble vascular endothelial growth factor receptor 1 (sFlt-1) in women by moderate exercise and increased plasma levels of vascular endothelial growth factor in overweight/obese women. Eur J Cancer Prev. 2012, 22: 83-89.CrossRef
28.
go back to reference Boodhwani M, Sodha NR, Mieno S, Ramlawi B, Xu SH, Feng J, Clements RT, Ruel M, Sellke FW: Insulin treatment enhances the myocardial angiogenic response in diabetes. J Thorac Cardiovasc Surg. 2007, 134: 1453-1460. 10.1016/j.jtcvs.2007.08.025. discussion 1460PubMedCentralCrossRefPubMed Boodhwani M, Sodha NR, Mieno S, Ramlawi B, Xu SH, Feng J, Clements RT, Ruel M, Sellke FW: Insulin treatment enhances the myocardial angiogenic response in diabetes. J Thorac Cardiovasc Surg. 2007, 134: 1453-1460. 10.1016/j.jtcvs.2007.08.025. discussion 1460PubMedCentralCrossRefPubMed
29.
go back to reference Sodha NR, Clements RT, Boodhwani M, Xu SH, Laham RJ, Bianchi C, Sellke FW: Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation. Am J Physiol Heart Circ Physiol. 2009, 296: H428-434.PubMedCentralCrossRefPubMed Sodha NR, Clements RT, Boodhwani M, Xu SH, Laham RJ, Bianchi C, Sellke FW: Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation. Am J Physiol Heart Circ Physiol. 2009, 296: H428-434.PubMedCentralCrossRefPubMed
30.
go back to reference Tenaglia AN, Peters KG, Sketch MH, Annex BH: Neovascularization in atherectomy specimens from patients with unstable angina: implications for pathogenesis of unstable angina. Am Heart J. 1998, 135: 10-14. 10.1016/S0002-8703(98)70336-9.CrossRefPubMed Tenaglia AN, Peters KG, Sketch MH, Annex BH: Neovascularization in atherectomy specimens from patients with unstable angina: implications for pathogenesis of unstable angina. Am Heart J. 1998, 135: 10-14. 10.1016/S0002-8703(98)70336-9.CrossRefPubMed
31.
go back to reference O'Brien ER, Garvin MR, Dev R, Stewart DK, Hinohara T, Simpson JB, Schwartz SM: Angiogenesis in human coronary atherosclerotic plaques. Am J Pathol. 1994, 145: 883-894.PubMedCentralPubMed O'Brien ER, Garvin MR, Dev R, Stewart DK, Hinohara T, Simpson JB, Schwartz SM: Angiogenesis in human coronary atherosclerotic plaques. Am J Pathol. 1994, 145: 883-894.PubMedCentralPubMed
32.
go back to reference Walsh K, Smith RC, Kim HS: Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res. 2000, 87: 184-188. 10.1161/01.RES.87.3.184.CrossRefPubMed Walsh K, Smith RC, Kim HS: Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res. 2000, 87: 184-188. 10.1161/01.RES.87.3.184.CrossRefPubMed
33.
go back to reference Mao W, Kong J, Dai J, Huang ZQ, Wang DZ, Ni GB, Chen ML: Evaluation of recombinant endostatin in the treatment of atherosclerotic plaques and neovascularization in rabbits. J Zhejiang Univ Sci B. 2010, 11: 599-607. 10.1631/jzus.B1001011.PubMedCentralCrossRefPubMed Mao W, Kong J, Dai J, Huang ZQ, Wang DZ, Ni GB, Chen ML: Evaluation of recombinant endostatin in the treatment of atherosclerotic plaques and neovascularization in rabbits. J Zhejiang Univ Sci B. 2010, 11: 599-607. 10.1631/jzus.B1001011.PubMedCentralCrossRefPubMed
34.
go back to reference Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J: Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation. 1999, 99: 1726-1732. 10.1161/01.CIR.99.13.1726.CrossRefPubMed Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J: Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation. 1999, 99: 1726-1732. 10.1161/01.CIR.99.13.1726.CrossRefPubMed
35.
go back to reference Wenzel D, Schmidt A, Reimann K, Hescheler J, Pfitzer G, Bloch W, Fleischmann BK: Endostatin, the proteolytic fragment of collagen XVIII, induces vasorelaxation. Circ Res. 2006, 98: 1203-1211. 10.1161/01.RES.0000219899.93384.ed.CrossRefPubMed Wenzel D, Schmidt A, Reimann K, Hescheler J, Pfitzer G, Bloch W, Fleischmann BK: Endostatin, the proteolytic fragment of collagen XVIII, induces vasorelaxation. Circ Res. 2006, 98: 1203-1211. 10.1161/01.RES.0000219899.93384.ed.CrossRefPubMed
Metadata
Title
Exercise increases serum endostatin levels in female and male patients with diabetes and controls
Authors
Michael Sponder
Daniela Dangl
Stephanie Kampf
Monika Fritzer-Szekeres
Jeanette Strametz-Juranek
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2014
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-13-6

Other articles of this Issue 1/2014

Cardiovascular Diabetology 1/2014 Go to the issue