https://doi.org/10.31288/oftalmolzh201835256

Activity of plasminogen activator inhibitor-1 in blood of patients with metabolic syndrome depending on a stage of diabetic retinopathy

Serdiuk V. N.,1 Dr Sc (Med); Kyryliuk M. L.,2 Dr Sc (Med), Prof.; Pylypenko L.Yu.,3 Post-grad Student, Ophthalmologist

1 Dnipropetrovsk Medical Academy, Health Ministry of Ukraine;  Dnipropetrovsk Regional Clinical Ophthalmology Hospital; Dnipro (Ukraine)

2 Ukrainian Research Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues, Health Ministry of Ukraine; Kyiv (Ukraine)

3 Dnipropetrovsk City Policlinics No4; Dnipro (Ukraine)

E-mail:  kzdokol@ukr.net, kmlazar@ukr.net, l-u-shevchenko@yandex.ua               

TO CITE THIS ARTICLE: Serdiuk VN, Kyryliuk ML, Pylypenko LYu. Activity of plasminogen activator inhibitor-1 in blood of patients with metabolic syndrome depending on a stage of diabetic retinopathy.  J.ophthalmol.(Ukraine).2018;3:52-56. https://doi.org/10.31288/oftalmolzh201835256

         

Background. The main cause for the development of proliferative diabetic retinopathy (DRP) is the absence of capillary perfusion, resulting in the initiation of retinal neovascularization. In ischemia reperfusion injury of the retina, the plasminogen activator inhibitor 1 (PAI-1), inflammatory mediators, cytokines, adhesion factors activated in the metabolic syndrome (MS) may be involved. Therefore, there is a necessity to evaluate the role of PAI-1 in the initiation and progression of DRP in MS.

Purpose. To study the activity of PAI-1 in blood of patients with the metabolic syndrome (MS) depending on a stage of diabetic retinopathy (DRP) and in relation with a level of circulating interleukin-8 (IL-8) and blood fibrinogen.

Material and Methods. Studies were carried out in 64 patients (95 eyes) with MS and DRP, comparable in sex, age and duration of type 2 diabetes mellitus (T2DM), which were divided into 3 groups depending on a stage of DRP. The control group consisted of 23 individuals of both sexes with obesity without T2DM. The activity of PAI-1 and the concentration of circulating IL-8 in blood were determined by enzyme immunoassay; fibrinogen was assessed by the clotting method. Statistical analysis included single-factor analysis of variance (ANOVA) and regression analysis.

Results. It was shown that only in the case of conditional combination of DRP stages II and III in one stage, the activity of PAI-1 was statistically significantly lower in comparison with the control group ((21.3 ± 2.8 U / ml (95% CI 17.3-25, 3) vs 12.0 ± 3.3 U / ml (95% CI 7.43-16.6), p < 0.05)), which did not occur in DRP stage (p> 0.05). In the group of patients with T2DM, regardless a stage of DRP, the level of PAI-1 activity was positively associated with circulating IL-8 concentration (r = 0.43, R2 = 18.6 %, N = 54, p = 0.001). Also, an inverse linear dependence of blood fibrinogen concentration on the PAI-1 activity was revealed (r = -0.36, R2 = 13.6%, N = 55, p = 0.005).

Conclusion. Patients with DRP and MS had significantly decreased PAI-1 at DRP stages II and III compared to non-diabetic obese patients (р<0.05) unlike the patients with DPR stage I (p>0.05); a strong significant positive association between PAI-1 and circulating IL-8 (p=0.001) and a significant negative linear relationship between blood fibrinogen concentration and PAI-1 (p=0.005) were revealed.

Keywords: diabetic retinopathy, metabolic syndrome, plasminogen activator inhibitor-1

References

1.Aisina RB, Mukhametova LI, Ostryakova EV et al. [Polymorphism of the plasminogen activator inhibitor type 1 gene, plasminogen level and thromboses in patients with the antiphospholipid syndrome]. Biochem. Moscow Suppl. Ser. B. 2013; 7(1):1-15. In Russian.
Crossref   Pubmed

2.Pasechnikova NV, Metelicyna IP, Naumenko VA, Beliaev VD. [Change in the level of some pro- and anti-inflammatory cytokines in patients with diabetic retinopathy after laser retinal coagulation]. Oftalmol Zh. 2010;2:4-7. In Russian.

3.Serdyuk VN, Ishhenko VA. [Morphometrial and biochemical clusters of metabolic syndrome in patients with type 2 diabetes mellitus at different stages of diabetic retinopathy]. Mizhnarodnyi endokrynolohichnyi zhurnal. 2016;7(79):69-74. In Russian.
Crossref

4.Alessi MC et al. Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes. 1997;46:860–7.
Crossref   Pubmed

5.Al-Hamodi, Z, et al. Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects. Cardiovasc Diabetol. 2011;10:23.
Crossref   Pubmed

6.Azad N, et al. VADT Study Group. Association of PAI-1 and fibrinogen with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT). J Clin Diagn Res. 2015 Jan;9(1):BC18-21. doi: 10.7860/JCDR/2015/10712.5449. 
Crossref   Pubmed

7.Das A, et al. Plasminogen Activator Inhibitor–1(PAI–1) in Early Diabetic Retinopathy and Retinal Neovascularization. Investigative Ophthalmology & Visual Science. 2005;46(13):2367.

8.Festa A. Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. The Insulin Resistance Atherosclerosis Study (IRAS). Arterioscler Thromb Vasc Biol. 1999;19:562–8.
Crossref   Pubmed

9.Follo M, Ginsburg D. “Structure and expression of the human gene encoding plasminogen activator inhibitor, PAI-1,” Gene, vol. 84, no. 2, pp. 447–453, 1989.
Crossref   Pubmed

10.Garner A. Histopathology of diabetic retinopathy in man. Eye. 1993;7(2):250–3. 
Crossref   Pubmed

11.Grant PJ. Diabetes mellitus as a prothrombotic condition. J Intern Med. 2007;262:157–72.
Crossref   Pubmed

12.Grundy SM, et al.  Diagnosis and Management of the Metabolic Syndrome. Circulation. 2005;112:2735–52.
Crossref   Pubmed

13.Liao H, Hyman MC, Lawrence DA, Pinsky DJ. Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1, HIF-1α, and C/EBPα. FASEB Journal. 2007;21(3):935–49. 
Crossref   Pubmed

14.Meigs JB, et al. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: The Framingham Offspring Study. JAMA. 2000;283:221–8.
Crossref   Pubmed

15.Nagi DK, et al.  Plasminogen Activator inhibitor (PAI-1) activity is elevated in asian and caucasian subjects with non-insulin-dependent (Type 2) Diabetes but not in those with impaired glucose tolerance (IGT) or non-diabetic Asians. Diabet Med. 1996;13:59–64.
Crossref   Pubmed

16.Sagel J, et al. Increased platelet aggregation in early diabetes mellitus. Ann Intern Med. 1975;82:733–8.
Crossref   Pubmed

17.Scott MG, et al. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-97.
Crossref   Pubmed 

18.Yan F, Pinsky DJ, Mackman N, Stern DM. Egr-1: is it always immediate and early? Journal of Clinical Investigation. 2000;105(5):553–4.
Crossref   Pubmed

19.Yarmolinsky J, et al. Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies. Sci Rep. 2016; 6:17714. doi: 10.1038/srep17714.
Crossref   Pubmed

20.Zhong Ze-Long, Chen Song. Plasma Plasminogen Activator Inhibitor-1 Is Associated with End-Stage Proliferative Diabetic Retinopathy in the Northern Chinese Han Population. Experimental Diabetes Research 2012;2012:Article ID 350852.