Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2011

Open Access 01-12-2011 | Original investigation

Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study

Authors: Sazan Rasul, Marie Helene Reiter, Aysegul Ilhan, Katharina Lampichler, Ludwig Wagner, Alexandra Kautzky-Willer

Published in: Cardiovascular Diabetology | Issue 1/2011

Login to get access

Abstract

Background

Type 2 diabetes is associated with increased levels of Angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie-2), but its impact on vascular disease is still unknown. This study aimed to further explore the associations of Ang-2 and sTie-2 with metabolic control and diabetic complications.

Methods

In a cross-sectional designed study, levels of Ang-2 and sTie-2 as well as their relationships to cardiometabolic parameters were determined in 80 type 2 diabetic subjects (age 65 ± 7 years, female 47.4%).

Results

After controlling for age and BMI, Ang-2 levels were associated with levels of sTie-2, diastolic blood pressure, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), creatinine, glomerular filtration rate (GFR), and gamma-glutamyl transferase (GGT) (all p < 0.02). Presence of diabetic macrovascular complications, polyneuropathy and insulin therapy were associated with higher Ang-2 levels (p < 0.05). Conversely, sTie-2 levels were associated with glycated hemoglobin (HbA1c), fasting plasma glucose and insulin, HOMA-IR, triglyceride, and liver function parameters (all p < 0.03). Multiple linear regression analysis showed that Ang-2 remained significantly associated only with levels of GGT (p < 0.04), whereas sTie-2 remained significantly associated with HbA 1c , insulin levels, and HOMA-IR (p < 0.03). No differences in Ang-2 and sTie-2 levels were observed with regard to gender of participants.

Conclusions

Ang-2 is independently associated with levels of GGT while sTie-2 is independently associated with levels of HbA 1c , plasma insulin and HOMA-IR in type 2 diabetic subjects. Therefore we suggest that the associations of Ang-2 and sTie-2 with type 2 diabetes are based on different patho-physiological mechanisms.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, McClain J, Martin C, Witte C, Witte MH, Jackson D: Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 2002, 3: 411-423. 10.1016/S1534-5807(02)00217-4.CrossRefPubMed Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, McClain J, Martin C, Witte C, Witte MH, Jackson D: Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 2002, 3: 411-423. 10.1016/S1534-5807(02)00217-4.CrossRefPubMed
2.
go back to reference Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD: Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996, 87: 1171-1180. 10.1016/S0092-8674(00)81813-9.CrossRefPubMed Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD: Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996, 87: 1171-1180. 10.1016/S0092-8674(00)81813-9.CrossRefPubMed
3.
go back to reference Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997, 277: 55-60. 10.1126/science.277.5322.55.CrossRefPubMed Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997, 277: 55-60. 10.1126/science.277.5322.55.CrossRefPubMed
4.
go back to reference Reusch P, Barleon B, Weindel K, Martiny-Baron G, Godde A, Siemeister G, Marme D: Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood. Angiogenesis. 2001, 4: 123-131. 10.1023/A:1012226627813.CrossRefPubMed Reusch P, Barleon B, Weindel K, Martiny-Baron G, Godde A, Siemeister G, Marme D: Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood. Angiogenesis. 2001, 4: 123-131. 10.1023/A:1012226627813.CrossRefPubMed
5.
go back to reference Hanahan D: Signaling vascular morphogenesis and maintenance. Science. 1997, 277: 48-50. 10.1126/science.277.5322.48.CrossRefPubMed Hanahan D: Signaling vascular morphogenesis and maintenance. Science. 1997, 277: 48-50. 10.1126/science.277.5322.48.CrossRefPubMed
6.
go back to reference Peters KG: Vascular endothelial growth factor and the angiopoietins: working together to build a better blood vessel. Circ Res. 1998, 83: 342-343.CrossRefPubMed Peters KG: Vascular endothelial growth factor and the angiopoietins: working together to build a better blood vessel. Circ Res. 1998, 83: 342-343.CrossRefPubMed
7.
go back to reference Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N: Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006, 12: 235-239. 10.1038/nm1351.CrossRefPubMed Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N: Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006, 12: 235-239. 10.1038/nm1351.CrossRefPubMed
8.
go back to reference Marti HH, Risau W: Angiogenesis in ischemic disease. Thromb Haemost. 1999, 82 (Suppl 1): 44-52.PubMed Marti HH, Risau W: Angiogenesis in ischemic disease. Thromb Haemost. 1999, 82 (Suppl 1): 44-52.PubMed
9.
go back to reference Nadar SK, Blann A, Beevers DG, Lip GY: Abnormal angiopoietins 1&2, angiopoietin receptor Tie-2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)]. J Intern Med. 2005, 258: 336-343. 10.1111/j.1365-2796.2005.01550.x.CrossRefPubMed Nadar SK, Blann A, Beevers DG, Lip GY: Abnormal angiopoietins 1&2, angiopoietin receptor Tie-2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)]. J Intern Med. 2005, 258: 336-343. 10.1111/j.1365-2796.2005.01550.x.CrossRefPubMed
10.
go back to reference Kumpers P, Nickel N, Lukasz A, Golpon H, Westerkamp V, Olsson KM, Jonigk D, Maegel L, Bockmeyer CL, David S: Circulating angiopoietins in idiopathic pulmonary arterial hypertension. Eur Heart J. 31: 2291-2300. Kumpers P, Nickel N, Lukasz A, Golpon H, Westerkamp V, Olsson KM, Jonigk D, Maegel L, Bockmeyer CL, David S: Circulating angiopoietins in idiopathic pulmonary arterial hypertension. Eur Heart J. 31: 2291-2300.
11.
go back to reference David S, Kumpers P, Lukasz A, Fliser D, Martens-Lobenhoffer J, Bode-Boger SM, Kliem V, Haller H, Kielstein JT: Circulating angiopoietin-2 levels increase with progress of chronic kidney disease. Nephrol Dial Transplant. 25: 2571-2576. David S, Kumpers P, Lukasz A, Fliser D, Martens-Lobenhoffer J, Bode-Boger SM, Kliem V, Haller H, Kielstein JT: Circulating angiopoietin-2 levels increase with progress of chronic kidney disease. Nephrol Dial Transplant. 25: 2571-2576.
12.
go back to reference DeBusk LM, Chen Y, Nishishita T, Chen J, Thomas JW, Lin PC: Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum. 2003, 48: 2461-2471. 10.1002/art.11213.CrossRefPubMed DeBusk LM, Chen Y, Nishishita T, Chen J, Thomas JW, Lin PC: Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum. 2003, 48: 2461-2471. 10.1002/art.11213.CrossRefPubMed
13.
go back to reference Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H, Yasui K, Takeuchi M, Makita Z, Takasawa S: Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2003, 370: 1097-1109. 10.1042/BJ20021371.PubMedCentralCrossRefPubMed Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H, Yasui K, Takeuchi M, Makita Z, Takasawa S: Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2003, 370: 1097-1109. 10.1042/BJ20021371.PubMedCentralCrossRefPubMed
14.
go back to reference Su J, Lucchesi PA, Gonzalez-Villalobos RA, Palen DI, Rezk BM, Suzuki Y, Boulares HA, Matrougui K: Role of advanced glycation end products with oxidative stress in resistance artery dysfunction in type 2 diabetic mice. Arterioscler Thromb Vasc Biol. 2008, 28: 1432-1438. 10.1161/ATVBAHA.108.167205.PubMedCentralCrossRefPubMed Su J, Lucchesi PA, Gonzalez-Villalobos RA, Palen DI, Rezk BM, Suzuki Y, Boulares HA, Matrougui K: Role of advanced glycation end products with oxidative stress in resistance artery dysfunction in type 2 diabetic mice. Arterioscler Thromb Vasc Biol. 2008, 28: 1432-1438. 10.1161/ATVBAHA.108.167205.PubMedCentralCrossRefPubMed
15.
go back to reference Tremolada G, Lattanzio R, Mazzolari G, Zerbini G: The therapeutic potential of VEGF inhibition in diabetic microvascular complications. Am J Cardiovasc Drugs. 2007, 7: 393-398. 10.2165/00129784-200707060-00002.CrossRefPubMed Tremolada G, Lattanzio R, Mazzolari G, Zerbini G: The therapeutic potential of VEGF inhibition in diabetic microvascular complications. Am J Cardiovasc Drugs. 2007, 7: 393-398. 10.2165/00129784-200707060-00002.CrossRefPubMed
16.
go back to reference Lim HS, Blann AD, Chong AY, Freestone B, Lip GY: Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes: implications for cardiovascular risk and effects of multifactorial intervention. Diabetes Care. 2004, 27: 2918-2924. 10.2337/diacare.27.12.2918.CrossRefPubMed Lim HS, Blann AD, Chong AY, Freestone B, Lip GY: Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes: implications for cardiovascular risk and effects of multifactorial intervention. Diabetes Care. 2004, 27: 2918-2924. 10.2337/diacare.27.12.2918.CrossRefPubMed
17.
go back to reference Lieb W, Zachariah JP, Xanthakis V, Safa R, Chen MH, Sullivan LM, Larson MG, Smith HM, Yang Q, Mitchell GF: Clinical and genetic correlates of circulating angiopoietin-2 and soluble Tie-2 in the community. Circ Cardiovasc Genet. 3: 300-306. Lieb W, Zachariah JP, Xanthakis V, Safa R, Chen MH, Sullivan LM, Larson MG, Smith HM, Yang Q, Mitchell GF: Clinical and genetic correlates of circulating angiopoietin-2 and soluble Tie-2 in the community. Circ Cardiovasc Genet. 3: 300-306.
18.
go back to reference Cai J, Kehoe O, Smith GM, Hykin P, Boulton ME: The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2008, 49: 2163-2171. 10.1167/iovs.07-1206.CrossRefPubMed Cai J, Kehoe O, Smith GM, Hykin P, Boulton ME: The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2008, 49: 2163-2171. 10.1167/iovs.07-1206.CrossRefPubMed
19.
go back to reference Anuradha S, Mohan V, Gokulakrishnan K, Dixit M: Angiopoietin-2 levels in glucose intolerance, hypertension, and metabolic syndrome in Asian Indians (Chennai Urban Rural Epidemiology Study-74). Metabolism. 59: 774-779. Anuradha S, Mohan V, Gokulakrishnan K, Dixit M: Angiopoietin-2 levels in glucose intolerance, hypertension, and metabolic syndrome in Asian Indians (Chennai Urban Rural Epidemiology Study-74). Metabolism. 59: 774-779.
20.
go back to reference Lim HS, Lip GY, Blann AD: Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005, 180: 113-118. 10.1016/j.atherosclerosis.2004.11.004.CrossRefPubMed Lim HS, Lip GY, Blann AD: Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005, 180: 113-118. 10.1016/j.atherosclerosis.2004.11.004.CrossRefPubMed
21.
go back to reference Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998, 15: 539-553. 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S.CrossRefPubMed Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998, 15: 539-553. 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S.CrossRefPubMed
22.
go back to reference Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F: Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006, 145: 247-254.CrossRefPubMed Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F: Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006, 145: 247-254.CrossRefPubMed
23.
go back to reference Pouyssegur J, Dayan F, Mazure NM: Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 2006, 441: 437-443. 10.1038/nature04871.CrossRefPubMed Pouyssegur J, Dayan F, Mazure NM: Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 2006, 441: 437-443. 10.1038/nature04871.CrossRefPubMed
24.
go back to reference De Palma M, Naldini L: Angiopoietin-2 TIEs Up Macrophages in Tumor Angiogenesis. Clin Cancer Res. 2011 De Palma M, Naldini L: Angiopoietin-2 TIEs Up Macrophages in Tumor Angiogenesis. Clin Cancer Res. 2011
25.
go back to reference Tuo QH, Zeng H, Stinnett A, Yu H, Aschner JL, Liao DF, Chen JX: Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol. 2008, 294: H2547-2557. 10.1152/ajpheart.01250.2007.CrossRefPubMed Tuo QH, Zeng H, Stinnett A, Yu H, Aschner JL, Liao DF, Chen JX: Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol. 2008, 294: H2547-2557. 10.1152/ajpheart.01250.2007.CrossRefPubMed
26.
go back to reference Pugliese G, Pricci F, Romeo G, Pugliese F, Mene P, Giannini S, Cresci B, Galli G, Rotella CM, Vlassara H: Upregulation of mesangial growth factor and extracellular matrix synthesis by advanced glycation end products via a receptor-mediated mechanism. Diabetes. 1997, 46: 1881-1887. 10.2337/diabetes.46.11.1881.CrossRefPubMed Pugliese G, Pricci F, Romeo G, Pugliese F, Mene P, Giannini S, Cresci B, Galli G, Rotella CM, Vlassara H: Upregulation of mesangial growth factor and extracellular matrix synthesis by advanced glycation end products via a receptor-mediated mechanism. Diabetes. 1997, 46: 1881-1887. 10.2337/diabetes.46.11.1881.CrossRefPubMed
27.
go back to reference Giacco F, Brownlee M: Oxidative stress and diabetic complications. Circ Res. 107: 1058-1070. Giacco F, Brownlee M: Oxidative stress and diabetic complications. Circ Res. 107: 1058-1070.
28.
go back to reference Okamoto T, Yamagishi S, Inagaki Y, Amano S, Koga K, Abe R, Takeuchi M, Ohno S, Yoshimura A, Makita Z: Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin. FASEB J. 2002, 16: 1928-1930.PubMed Okamoto T, Yamagishi S, Inagaki Y, Amano S, Koga K, Abe R, Takeuchi M, Ohno S, Yoshimura A, Makita Z: Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin. FASEB J. 2002, 16: 1928-1930.PubMed
29.
go back to reference Lobov IB, Brooks PC, Lang RA: Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA. 2002, 99: 11205-11210. 10.1073/pnas.172161899.PubMedCentralCrossRefPubMed Lobov IB, Brooks PC, Lang RA: Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA. 2002, 99: 11205-11210. 10.1073/pnas.172161899.PubMedCentralCrossRefPubMed
30.
go back to reference Drozdz R, Parmentier C, Hachad H, Leroy P, Siest G, Wellman M: gamma-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med. 1998, 25: 786-792. 10.1016/S0891-5849(98)00127-0.CrossRefPubMed Drozdz R, Parmentier C, Hachad H, Leroy P, Siest G, Wellman M: gamma-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med. 1998, 25: 786-792. 10.1016/S0891-5849(98)00127-0.CrossRefPubMed
31.
go back to reference Takigawa T, Hibino Y, Kimura S, Yamauchi H, Wang B, Wang D, Ogino K: Association between serum gamma-glutamyltransferase and oxidative stress related factors. Hepatogastroenterology. 2008, 55: 50-53.PubMed Takigawa T, Hibino Y, Kimura S, Yamauchi H, Wang B, Wang D, Ogino K: Association between serum gamma-glutamyltransferase and oxidative stress related factors. Hepatogastroenterology. 2008, 55: 50-53.PubMed
32.
go back to reference Lim JS, Yang JH, Chun BY, Kam S, Jacobs DR, Lee DH: Is serum gamma-glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress?. Free Radic Biol Med. 2004, 37: 1018-1023. 10.1016/j.freeradbiomed.2004.06.032.CrossRefPubMed Lim JS, Yang JH, Chun BY, Kam S, Jacobs DR, Lee DH: Is serum gamma-glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress?. Free Radic Biol Med. 2004, 37: 1018-1023. 10.1016/j.freeradbiomed.2004.06.032.CrossRefPubMed
33.
go back to reference Lee DH, Silventoinen K, Hu G, Jacobs DR, Jousilahti P, Sundvall J, Tuomilehto J: Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. Eur Heart J. 2006, 27: 2170-2176. 10.1093/eurheartj/ehl086.CrossRefPubMed Lee DH, Silventoinen K, Hu G, Jacobs DR, Jousilahti P, Sundvall J, Tuomilehto J: Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. Eur Heart J. 2006, 27: 2170-2176. 10.1093/eurheartj/ehl086.CrossRefPubMed
34.
go back to reference Shankar A, Li J: Association between serum gamma-glutamyltransferase level and prehypertension among US adults. Circ J. 2007, 71: 1567-1572. 10.1253/circj.71.1567.CrossRefPubMed Shankar A, Li J: Association between serum gamma-glutamyltransferase level and prehypertension among US adults. Circ J. 2007, 71: 1567-1572. 10.1253/circj.71.1567.CrossRefPubMed
35.
go back to reference Matsui T, Nishino Y, Takeuchi M, Yamagishi S: Vildagliptin blocks vascular injury in thoracic aorta of diabetic rats by suppressing advanced glycation end product-receptor axis. Pharmacol Res. 63: 383-388. Matsui T, Nishino Y, Takeuchi M, Yamagishi S: Vildagliptin blocks vascular injury in thoracic aorta of diabetic rats by suppressing advanced glycation end product-receptor axis. Pharmacol Res. 63: 383-388.
36.
go back to reference Rajesh M, Mukhopadhyay P, Batkai S, Patel V, Saito K, Matsumoto S, Kashiwaya Y, Horvath B, Mukhopadhyay B, Becker L: Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol. 56: 2115-2125. Rajesh M, Mukhopadhyay P, Batkai S, Patel V, Saito K, Matsumoto S, Kashiwaya Y, Horvath B, Mukhopadhyay B, Becker L: Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol. 56: 2115-2125.
37.
go back to reference Biscetti F, Straface G, Arena V, Stigliano E, Pecorini G, Rizzo P, De Angelis G, Iuliano L, Ghirlanda G, Flex A: Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARgamma stimulation. Cardiovasc Diabetol. 2009, 8: 49-10.1186/1475-2840-8-49.PubMedCentralCrossRefPubMed Biscetti F, Straface G, Arena V, Stigliano E, Pecorini G, Rizzo P, De Angelis G, Iuliano L, Ghirlanda G, Flex A: Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARgamma stimulation. Cardiovasc Diabetol. 2009, 8: 49-10.1186/1475-2840-8-49.PubMedCentralCrossRefPubMed
38.
go back to reference Peters KG, Kontos CD, Lin PC, Wong AL, Rao P, Huang L, Dewhirst MW, Sankar S: Functional significance of Tie2 signaling in the adult vasculature. Recent Prog Horm Res. 2004, 59: 51-71. 10.1210/rp.59.1.51.CrossRefPubMed Peters KG, Kontos CD, Lin PC, Wong AL, Rao P, Huang L, Dewhirst MW, Sankar S: Functional significance of Tie2 signaling in the adult vasculature. Recent Prog Horm Res. 2004, 59: 51-71. 10.1210/rp.59.1.51.CrossRefPubMed
39.
go back to reference Rupnick MA, Panigrahy D, Zhang CY, Dallabrida SM, Lowell BB, Langer R, Folkman MJ: Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci USA. 2002, 99: 10730-10735. 10.1073/pnas.162349799.PubMedCentralCrossRefPubMed Rupnick MA, Panigrahy D, Zhang CY, Dallabrida SM, Lowell BB, Langer R, Folkman MJ: Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci USA. 2002, 99: 10730-10735. 10.1073/pnas.162349799.PubMedCentralCrossRefPubMed
40.
go back to reference Nakayama T, Hatachi G, Wen CY, Yoshizaki A, Yamazumi K, Niino D, Sekine I: Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2 and 4 in colorectal adenocarcinoma: Immunohistochemical analysis and correlation with clinicopathological factors. World J Gastroenterol. 2005, 11: 964-969.PubMedCentralCrossRefPubMed Nakayama T, Hatachi G, Wen CY, Yoshizaki A, Yamazumi K, Niino D, Sekine I: Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2 and 4 in colorectal adenocarcinoma: Immunohistochemical analysis and correlation with clinicopathological factors. World J Gastroenterol. 2005, 11: 964-969.PubMedCentralCrossRefPubMed
41.
go back to reference Lee KW, Lip GY, Blann AD: Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes. Circulation. 2004, 110: 2355-2360. 10.1161/01.CIR.0000138112.90641.7F.CrossRefPubMed Lee KW, Lip GY, Blann AD: Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes. Circulation. 2004, 110: 2355-2360. 10.1161/01.CIR.0000138112.90641.7F.CrossRefPubMed
42.
go back to reference Defronzo RA: Is insulin resistance atherogenic? Possible mechanisms. Atheroscler Suppl. 2006, 7: 11-15.CrossRefPubMed Defronzo RA: Is insulin resistance atherogenic? Possible mechanisms. Atheroscler Suppl. 2006, 7: 11-15.CrossRefPubMed
43.
go back to reference Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000, 321: 405-412. 10.1136/bmj.321.7258.405.PubMedCentralCrossRefPubMed Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000, 321: 405-412. 10.1136/bmj.321.7258.405.PubMedCentralCrossRefPubMed
44.
go back to reference Ye F, Florian M, Magder SA, Hussain SN: Regulation of angiopoietin and Tie-2 receptor expression in non-reproductive tissues by estrogen. Steroids. 2002, 67: 305-310. 10.1016/S0039-128X(01)00163-5.CrossRefPubMed Ye F, Florian M, Magder SA, Hussain SN: Regulation of angiopoietin and Tie-2 receptor expression in non-reproductive tissues by estrogen. Steroids. 2002, 67: 305-310. 10.1016/S0039-128X(01)00163-5.CrossRefPubMed
Metadata
Title
Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study
Authors
Sazan Rasul
Marie Helene Reiter
Aysegul Ilhan
Katharina Lampichler
Ludwig Wagner
Alexandra Kautzky-Willer
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2011
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-10-55

Other articles of this Issue 1/2011

Cardiovascular Diabetology 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.