Plasminogen Activator Inhibitor-1 and Metabolic Disorders

Plasminogen Activator Inhibitor-1 (PAI-1) is the principal regulator of fibrinolysis, acting as a serine protease inhibitor that controls the activity of tissue plasminogen activator and urokinase-type plasminogen activator. In healthy physiology, balanced PAI-1 expression ensures effective clot dissolution and vascular integrity. However, in metabolic disorders such as obesity, insulin resistance and type 2 diabetes, PAI-1 levels are often elevated, contributing to a hypofibrinolytic state and increased thrombotic risk. Mechanistically, proinflammatory cytokines and hyperinsulinaemia upregulate PAI-1 synthesis in adipose tissue, linking chronic low-grade inflammation to impaired vascular function. Epidemiological evidence supports an association between high circulating PAI-1 and adverse cardiometabolic outcomes, including accelerated atherosclerosis and coronary heart disease. Emerging research has illuminated the interplay between PAI-1, metabolic homeostasis and inter-organ communication, positioning PAI-1 both as a biomarker of disease severity and as a potential therapeutic target in metabolic syndrome.

Research from Nature Portfolio

A comprehensive systematic review and meta-analysis of observational studies has reinforced the link between elevated PAI-1 levels and incident type 2 diabetes. By pooling data from multiple cohorts, the analysis demonstrated that individuals in the highest tertile of baseline PAI-1 faced a substantially increased risk of diabetes onset, independent of traditional risk factors such as adiposity and dyslipidaemia. This work established the epidemiological robustness of PAI-1 as a marker of glucose dysregulation and highlighted its potential utility in risk stratification.

Plasminogen Activator Inhibitor-1 and Metabolic Disorders publication trend

The graph below shows the total number of articles in plasminogen activator inhibitor-1 and metabolic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Plasminogen Activator Inhibitor-1 (PAI-1): A serine protease inhibitor that regulates the breakdown of blood clots by inhibiting fibrinolysis.

Fibrinolysis: The enzymatic process that degrades fibrin networks in blood clots to maintain vascular patency.

Insulin Resistance: A metabolic state in which target tissues exhibit diminished response to insulin, impairing glucose uptake.

Adipokine: A signalling protein secreted by adipose tissue that mediates communication between adipose depots and other organs.

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR): A calculation based on fasting glucose and insulin used to estimate insulin sensitivity.

References

1. Blood coagulation in Prediabetes clusters–impact on all-cause mortality in individuals undergoing coronary angiography. Cardiovascular Diabetology (2024).
2. The role of fibrinolysis in the development of prediabetes-associated coronary heart disease: a focus on the plasminogen activator inhibitor -1 and its potential use as a predictive marker in diet-induced prediabetes. Frontiers in Nutrition (2023).
3. Efficacy of Probiotic Strains Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 in Management of Obesity: An In Vitro and In Vivo Analysis. Pharmaceuticals (2024).
4. Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication. Journal of Lipid Research (2019).
5. Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies. Scientific Reports (2016).
6. Association between plasminogen activator inhibitor-1 and cardiovascular events: a systematic review and meta-analysis. Thrombosis Journal (2018).
7. PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target. International Journal of Molecular Sciences (2021).