Endocrinol Metab.  2017 Mar;32(1):99-105. 10.3803/EnM.2017.32.1.99.

Vascular Cell Adhesion Molecule 1, Intercellular Adhesion Molecule 1, and Cluster of Differentiation 146 Levels in Patients with Type 2 Diabetes with Complications

• Hocaoglu-Emre FS
• Saribal D
• Yenmis G
• Guvenen G

• KMID: 2413293
• DOI: http://doi.org/10.3803/EnM.2017.32.1.99

Abstract

BACKGROUND
Type 2 diabetes mellitus (T2DM) is a multisystemic, chronic disease accompanied by microvascular complications involving various complicated mechanisms. Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and cluster of differentiation-146 (CD146) are mainly expressed by endothelial cells, and facilitate the adhesion and transmigration of immune cells, leading to inflammation. In the present study, we evaluated the levels of soluble adhesion molecules in patients with microvascular complications of T2DM.
METHODS
Serum and whole blood samples were collected from 58 T2DM patients with microvascular complications and 20 age-matched healthy subjects. Levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) were assessed using enzyme-linked immunosorbent assay, while flow cytometry was used to determine CD146 levels.
RESULTS
Serum sICAM-1 levels were lower in T2DM patients with microvascular complications than in healthy controls (P<0.05). No significant differences were found in sVCAM-1 and CD146 levels between the study and the control group. Although patients were subdivided into groups according to the type of microvascular complications that they experienced, cell adhesion molecule levels were not correlated with the complication type.
CONCLUSION
In the study group, most of the patients were on insulin therapy (76%), and 95% of them were receiving angiotensin-converting enzyme (ACE)-inhibitor agents. Insulin and ACE-inhibitors have been shown to decrease soluble adhesion molecule levels via various mechanisms, so we suggest that the decreased or unchanged levels of soluble forms of cellular adhesion molecules in our study group may have resulted from insulin and ACE-inhibitor therapy, as well as tissue-localized inflammation in patients with T2DM.

Keyword

Cell adhesion molecules; CD146; Diabetes mellitus; Intercellular adhesion molecule-1; Microvascular complications; Vascular cell adhesion molecule-1

MeSH Terms

Cell Adhesion
Cell Adhesion Molecules
Chronic Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Healthy Volunteers
Humans
Inflammation
Insulin
Intercellular Adhesion Molecule-1
Vascular Cell Adhesion Molecule-1*
Cell Adhesion Molecules
Insulin
Intercellular Adhesion Molecule-1
Vascular Cell Adhesion Molecule-1

Reference

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37:Suppl 1. S81–S90.

2. Stratton IM, Kohner EM, Aldington SJ, Turner RC, Holman RR, Manley SE, et al. UKPDS 50: risk factors for incidence and progression of retinopathy in type II diabetes over 6 years from diagnosis. Diabetologia. 2001; 44:156–163.

3. Haneda M, Utsunomiya K, Koya D, Babazono T, Moriya T, Makino H, et al. A new classification of diabetic nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy. J Diabetes Investig. 2015; 6:242–246.

4. Golias C, Tsoutsi E, Matziridis A, Makridis P, Batistatou A, Charalabopoulos K. Review. Leukocyte and endothelial cell adhesion molecules in inflammation focusing on inflammatory heart disease. In Vivo. 2007; 21:757–769.

5. Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006; 6:508–519.

6. Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol. 2001; 158:147–152.

7. Hadi HA, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007; 3:853–876.

8. Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004; 15:1983–1992.

9. Aricescu AR, Jones EY. Immunoglobulin superfamily cell adhesion molecules: zippers and signals. Curr Opin Cell Biol. 2007; 19:543–550.

10. Chen C, Mobley JL, Dwir O, Shimron F, Grabovsky V, Lobb RR, et al. High affinity very late antigen-4 subsets expressed on T cells are mandatory for spontaneous adhesion strengthening but not for rolling on VCAM-1 in shear flow. J Immunol. 1999; 162:1084–1095.

11. Schnoor M, Alcaide P, Voisin MB, van Buul JD. Crossing the vascular wall: common and unique mechanisms exploited by different leukocyte subsets during extravasation. Mediators Inflamm. 2015; 2015:946509.

12. Liu JJ, Yeoh LY, Sum CF, Tavintharan S, Ng XW, Liu S, et al. Vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1, is associated with diabetic kidney disease in Asians with type 2 diabetes. J Diabetes Complications. 2015; 29:707–712.

13. Noda K, Nakao S, Zandi S, Sun D, Hayes KC, Hafezi-Moghadam A. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm. FASEB J. 2014; 28:2038–2046.

14. Goldberg RB. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab. 2009; 94:3171–3182.

15. Lin J, Glynn RJ, Rifai N, Manson JE, Ridker PM, Nathan DM, et al. Inflammation and progressive nephropathy in type 1 diabetes in the diabetes control and complications trial. Diabetes Care. 2008; 31:2338–2343.

16. Persson F, Rossing P, Hovind P, Stehouwer CD, Schalkwijk CG, Tarnow L, et al. Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in patients with type 2 diabetes and microalbuminuria (IRMA 2) study. Scand J Clin Lab Invest. 2008; 68:731–738.

17. Lu J, Randell E, Han Y, Adeli K, Krahn J, Meng QH. Increased plasma methylglyoxal level, inflammation, and vascular endothelial dysfunction in diabetic nephropathy. Clin Biochem. 2011; 44:307–311.

18. Ruszkowska-Ciastek B, Sokup A, Wernik T, Ruprecht Z, Goralczyk B, Goralczyk K, et al. Effect of uncontrolled hyperglycemia on levels of adhesion molecules in patients with diabetes mellitus type 2. J Zhejiang Univ Sci B. 2015; 16:355–361.

19. Ugurlu N, Gerceker S, Yulek F, Ugurlu B, Sari C, Baran P, et al. The levels of the circulating cellular adhesion molecules ICAM-1, VCAM-1 and endothelin-1 and the flow-mediated vasodilatation values in patients with type 1 diabetes mellitus with early-stage diabetic retinopathy. Intern Med. 2013; 52:2173–2178.

20. Wang F, Xing T, Wang N, Liu L. Clinical significance of plasma CD146 and P-selectin in patients with type 2 diabetic nephropathy. Cytokine. 2012; 57:127–129.

21. Luis-Rodriguez D, Martinez-Castelao A, Gorriz JL, De-Alvaro F, Navarro-Gonzalez JF. Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy. World J Diabetes. 2012; 3:7–18.

22. Guler S, Cakir B, Demirbas B, Yonem A, Odabasi E, Onde U, et al. Plasma soluble intercellular adhesion molecule 1 levels are increased in type 2 diabetic patients with nephropathy. Horm Res. 2002; 58:67–70.

23. Kanasaki K, Taduri G, Koya D. Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis. Front Endocrinol (Lausanne). 2013; 4:7.

24. Matsumoto K, Sera Y, Ueki Y, Inukai G, Niiro E, Miyake S. Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy. Diabet Med. 2002; 19:822–826.

25. Aljada A, Saadeh R, Assian E, Ghanim H, Dandona P. Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide. J Clin Endocrinol Metab. 2000; 85:2572–2575.

26. De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA Jr, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest. 1995; 96:60–68.

27. Drexler H, Kurz S, Jeserich M, Munzel T, Hornig B. Effect of chronic angiotensin-converting enzyme inhibition on endothelial function in patients with chronic heart failure. Am J Cardiol. 1995; 76:13E–18E.

28. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005; 96:939–949.