Circulating Angiopoietin-2 and Soluble Tie-2 in Type 2 Diabetes Mellitus: a Cross-sectional Study

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2011 Jun 25

PMID 21699724

Citations 26

Authors

Sazan Rasul

Marie Helene Reiter

Aysegul Ilhan

Katharina Lampichler

Ludwig Wagner

Alexandra Kautzky-Willer

Affiliations

Soon will be listed here.

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.

Citing Articles

Serum angiopoietin-2/angiopoietin-1 ratio is associated with cardiovascular and all-cause mortality in peritoneal dialysis patients: a prospective cohort study.

Li H, Song Q, Su X, Shen Y, Yan H, Yu Z Ren Fail. 2024; 46(2):2380037.

PMID: 39082686 PMC: 11293270. DOI: 10.1080/0886022X.2024.2380037.

Serum angiopoietin-2: a promising biomarker for early diabetic kidney disease in children and adolescents with type 1 diabetes.

Salem N, Ismail W, Hendawy S, Abdelrahman A, El-Refaey A Eur J Pediatr. 2024; 183(9):3853-3862.

PMID: 38884820 PMC: 11322226. DOI: 10.1007/s00431-024-05637-w.

Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap-a cross-sectional study.

Matovu Dungu A, Lundgaard A, Ryrso C, Hegelund M, Jensen A, Kristensen P Front Immunol. 2024; 15:1372300.

PMID: 38840922 PMC: 11150596. DOI: 10.3389/fimmu.2024.1372300.

Diabetes and further risk of cancer: a nationwide population-based study.

Chang W, Hsieh T, Hsu W, Chang F, Tsai H, He M BMC Med. 2024; 22(1):214.

PMID: 38807177 PMC: 11134680. DOI: 10.1186/s12916-024-03430-y.

Peripheral sensory neuropathy is associated with circulating angiopoietins in type 2 diabetes patients in Ghana.

Agyekum J, Yeboah K J Clin Transl Endocrinol. 2023; 34:100327.

PMID: 37822668 PMC: 10563058. DOI: 10.1016/j.jcte.2023.100327.

References

Peters K, Kontos C, Lin P, Wong A, Rao P, Huang L . Functional significance of Tie2 signaling in the adult vasculature. Recent Prog Horm Res. 2004; 59:51-71. DOI: 10.1210/rp.59.1.51. View

DeBusk L, Chen Y, Nishishita T, Chen J, Thomas J, Lin P . Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum. 2003; 48(9):2461-71. DOI: 10.1002/art.11213. View

Okamoto T, Yamagishi S, Inagaki Y, Amano S, Koga K, Abe R . Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin. FASEB J. 2002; 16(14):1928-30. DOI: 10.1096/fj.02-0030fje. View

Lieb W, Zachariah J, Xanthakis V, Safa R, Chen M, Sullivan L . Clinical and genetic correlates of circulating angiopoietin-2 and soluble Tie-2 in the community. Circ Cardiovasc Genet. 2010; 3(3):300-6. PMC: 2892960. DOI: 10.1161/CIRCGENETICS.109.914556. View

Kumpers P, Nickel N, Lukasz A, Golpon H, Westerkamp V, Olsson K . Circulating angiopoietins in idiopathic pulmonary arterial hypertension. Eur Heart J. 2010; 31(18):2291-300. DOI: 10.1093/eurheartj/ehq226. View

Stratton I, Adler A, Neil H, Matthews D, Manley S, Cull C . Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000; 321(7258):405-12. PMC: 27454. DOI: 10.1136/bmj.321.7258.405. View

Lobov I, Brooks P, Lang R . Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci U S A. 2002; 99(17):11205-10. PMC: 123234. DOI: 10.1073/pnas.172161899. View

Shankar A, Li J . Association between serum gamma-glutamyltransferase level and prehypertension among US adults. Circ J. 2007; 71(10):1567-72. DOI: 10.1253/circj.71.1567. View

Su J, Lucchesi P, Gonzalez-Villalobos R, Palen D, Rezk B, Suzuki Y . Role of advanced glycation end products with oxidative stress in resistance artery dysfunction in type 2 diabetic mice. Arterioscler Thromb Vasc Biol. 2008; 28(8):1432-8. PMC: 2755261. DOI: 10.1161/ATVBAHA.108.167205. View

10.

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. 2011; 63(5):383-8. DOI: 10.1016/j.phrs.2011.02.003. View

11.

Tuo Q, Zeng H, Stinnett A, Yu H, Aschner J, Liao D . Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol. 2008; 294(6):H2547-57. DOI: 10.1152/ajpheart.01250.2007. View

12.

Hanahan D . Signaling vascular morphogenesis and maintenance. Science. 1997; 277(5322):48-50. DOI: 10.1126/science.277.5322.48. View

13.

Biscetti F, Straface G, Arena V, Stigliano E, Pecorini G, Rizzo P . 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. PMC: 2745363. DOI: 10.1186/1475-2840-8-49. View

14.

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. 2009; 59(6):774-9. DOI: 10.1016/j.metabol.2009.09.022. View

15.

Maisonpierre P, Suri C, Jones P, Bartunkova S, Wiegand S, Radziejewski C . Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997; 277(5322):55-60. DOI: 10.1126/science.277.5322.55. View

16.

Rajesh M, Mukhopadhyay P, Batkai S, Patel V, Saito K, Matsumoto S . Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol. 2010; 56(25):2115-25. PMC: 3026637. DOI: 10.1016/j.jacc.2010.07.033. View

17.

Suri C, Jones P, Patan S, Bartunkova S, Maisonpierre P, Davis S . Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996; 87(7):1171-80. DOI: 10.1016/s0092-8674(00)81813-9. View

18.

Marti H, Risau W . Angiogenesis in ischemic disease. Thromb Haemost. 2000; 82 Suppl 1:44-52. View

19.

Yonekura H, Yamamoto Y, Sakurai S, Petrova R, Abedin M, Li H . 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. 2002; 370(Pt 3):1097-109. PMC: 1223244. DOI: 10.1042/BJ20021371. View

20.

Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G . Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006; 12(2):235-9. DOI: 10.1038/nm1351. View