Association of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator with Type 2 Diabetes and Metabolic Syndrome in Malaysian Subjects

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2011 Mar 19

PMID 21414238

Citations 19

Authors

Zaid Al-Hamodi

Ikram S Ismail

Riyadh Saif-Ali

Khaled A Ahmed

Sekaran Muniandy

Affiliations

Soon will be listed here.

Abstract

Background: Increased plasma plasminogen activator inhibitor-1 (PAI-1) activity and decreased tissue plasminogen activator (tPA) activity could be considered a true component of the metabolic syndrome (MetS) associated with an increased risk of developing cardiovascular diseases (CVD) and fibrinolytic abnormalities. The aim of this study was to investigate the association of tPA and its inhibitor PAI-1 with type 2 diabetes (T2D) and MetS and interrelationship between PAI-1 and tPA activities and antigens in Malaysian T2D and normal subjects.

Methods: The plasma activities and antigens of PAI-1 and tPA and the levels of the tPA/PAI-1 complex as well as serum insulin, parameter of the coronary risk panel and plasma glucose at fasting state were studied in 303 T2D subjects (227 with MetS and 76 without MetS), 131 normal non-diabetic non-metabolic subjects and 101 non-diabetic MetS subjects.

Results: The PAI-1 activity was higher in subjects with T2D with MetS (P = 9.8 × 10⁻¹⁹) and non-diabetic subjects with MetS (P = 3.0 × 10⁻¹⁵), whereas the tPA activity was lower in T2D with MetS (P = 0.003) as compare to normal subjects. Plasma tPA antigen levels were higher in subjects with T2D with MetS (P = 8.9 × 10⁻²⁴), T2D without MetS (P = 1.3 × 10⁻¹³) and non-diabetic MetS subjects (P = 0.002). The activity and antigen of PAI-1 in normal subjects were related to insulin resistance (P = 2.2 × 10⁻⁴; 0.007). Additionally, the PAI-1 activity was associated with an increased waist circumference (P = 2.2 × 10⁻⁴) and decreased HDL-c (P = 0.005), whereas the tPA activity was associated with decreased FBG (P = 0.028). The highest correlation was between PAI-1 activity and its antigen (R² = 0.695, P = 1.1 × 10⁻³⁶) in diabetic subjects. The tPA activity negatively correlated with its antigen (R² = -0.444, P = 7.7 × 10⁻¹³) in normal subjects and with the PAI-1 activity and antigen (R² = -0.319, P = 9.9 × 10⁻¹²; R² = -0.228, P = 3.4 × 10⁻⁶) in diabetic subjects.

Conclusions: PAI-1 and tPA activities and antigens were associated with diabetes and MetS parameters in Malaysian subjects.

Citing Articles

Elevated levels of PAI-1 precede the occurrence of type 2 diabetes mellitus.

Hernestal-Boman J, Ohman T, Jansson J, Lind M, Rolandsson O, Bergdahl I Diabetol Metab Syndr. 2025; 17(1):61.

PMID: 39966987 PMC: 11834294. DOI: 10.1186/s13098-025-01629-4.

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

Zhang Z, Dai W, Zhu W, Rodriguez M, Lund H, Xia Y Res Pract Thromb Haemost. 2023; 7(6):102164.

PMID: 37680312 PMC: 10480648. DOI: 10.1016/j.rpth.2023.102164.

Serum lipoprotein(a), and plasminogen activator inhibitor-1 in uncomplicated type 2 diabetes mellitus: a case-control study.

Abdullah F, Ahmed S Ann Med Surg (Lond). 2023; 85(8):3801-3805.

PMID: 37554894 PMC: 10405991. DOI: 10.1097/MS9.0000000000000915.

Relationship between serum and tear levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in diabetic retinopathy.

Jasmiad N, Abd Ghani R, Agarwal R, Ismail Z, Mohd Abdullah A, Idorus M BMC Ophthalmol. 2022; 22(1):357.

PMID: 36057550 PMC: 9441077. DOI: 10.1186/s12886-022-02550-4.

Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome.

Khasanova A, Dobrodeeva V, Shnayder N, Petrova M, Pronina E, Bochanova E Metabolites. 2022; 12(8).

PMID: 36005598 PMC: 9416438. DOI: 10.3390/metabo12080726.

References

Cavallero E, Dachet C, Assadolahi F, Martin C, Navarro N, Ansquer J . Micronized fenofibrate normalizes the enhanced lipidemic response to a fat load in patients with type 2 diabetes and optimal glucose control. Atherosclerosis. 2002; 166(1):151-61. DOI: 10.1016/s0021-9150(02)00321-0. View

Glowinska B, Urban M, Koput A, Galar M . New atherosclerosis risk factors in obese, hypertensive and diabetic children and adolescents. Atherosclerosis. 2003; 167(2):275-86. DOI: 10.1016/s0021-9150(03)00003-0. View

Sahli D, Eriksson J, Boman K, Svensson M . Tissue plasminogen activator (tPA) activity is a novel and early marker of asymptomatic LEAD in type 2 diabetes. Thromb Res. 2008; 123(5):701-6. DOI: 10.1016/j.thromres.2008.07.015. View

Auwerx J, Bouillon R, Collen D, Geboers J . Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis. 1988; 8(1):68-72. DOI: 10.1161/01.atv.8.1.68. View

Prabhakaran D, Anand S . The metabolic syndrome: an emerging risk state for cardiovascular disease. Vasc Med. 2004; 9(1):55-68. DOI: 10.1191/1358863x04vm515ra. View

Anand S, Yi Q, Gerstein H, Lonn E, Jacobs R, Vuksan V . Relationship of metabolic syndrome and fibrinolytic dysfunction to cardiovascular disease. Circulation. 2003; 108(4):420-5. DOI: 10.1161/01.CIR.0000080884.27358.49. View

Sobel B, Tilton L, Neimane D, Schnure J . Increased tissue-type plasminogen activator: a facade in the fibrinolytic system in type 2 diabetes. Coron Artery Dis. 2005; 16(1):31-5. DOI: 10.1097/00019501-200502000-00006. View

Alessi M, Poggi M, Juhan-Vague I . Plasminogen activator inhibitor-1, adipose tissue and insulin resistance. Curr Opin Lipidol. 2007; 18(3):240-5. DOI: 10.1097/MOL.0b013e32814e6d29. View

Morioka S, Makino H, Shikata K, Ota Z . Changes in plasma concentrations of vitronectin in patients with diabetic nephropathy. Acta Med Okayama. 1994; 48(3):137-42. DOI: 10.18926/AMO/31126. View

10.

Juhan-Vague I, Pyke S, Alessi M, Jespersen J, Haverkate F, Thompson S . Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation. 1996; 94(9):2057-63. DOI: 10.1161/01.cir.94.9.2057. View

11.

Ma L, Mao S, Taylor K, Kanjanabuch T, Guan Y, Zhang Y . Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes. 2004; 53(2):336-46. DOI: 10.2337/diabetes.53.2.336. View

12.

Juhan-Vague I, Alessi M . Plasminogen activator inhibitor 1 and atherothrombosis. Thromb Haemost. 1993; 70(1):138-43. View

13.

Wiman B, Almquist A, Sigurdardottir O, Lindahl T . Plasminogen activator inhibitor 1 (PAI) is bound to vitronectin in plasma. FEBS Lett. 1988; 242(1):125-8. DOI: 10.1016/0014-5793(88)80999-2. View

14.

Goldberg R . Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab. 2009; 94(9):3171-82. DOI: 10.1210/jc.2008-2534. View

15.

Ladenvall P, Johansson L, Jansson J, Jern S, Nilsson T, Tjarnlund A . Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction. Thromb Haemost. 2002; 87(1):105-9. View

16.

Lempiainen P, Mykkanen L, Pyorala K, Laakso M, Kuusisto J . Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men. Circulation. 1999; 100(2):123-8. DOI: 10.1161/01.cir.100.2.123. View

17.

Zimmet P, Alberti K, Shaw J . Global and societal implications of the diabetes epidemic. Nature. 2001; 414(6865):782-7. DOI: 10.1038/414782a. View

18.

Lijnen H . Pleiotropic functions of plasminogen activator inhibitor-1. J Thromb Haemost. 2005; 3(1):35-45. DOI: 10.1111/j.1538-7836.2004.00827.x. View

19.

Lapolla A, Piarulli F, Sartore G, Rossetti C, Martano L, Carraro P . Peripheral artery disease in type 2 diabetes: the role of fibrinolysis. Thromb Haemost. 2003; 89(1):91-6. View

20.

Arnlov J, Ingelsson E, Sundstrom J, Lind L . Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2009; 121(2):230-6. DOI: 10.1161/CIRCULATIONAHA.109.887521. View