Plasminogen Activator Inhibitor‐1 and Diagnosis of the Metabolic Syndrome in a West African Population

Abstract

BackgroundMetabolic syndrome (MetS) is diagnosed by the presence of at least 3 of the following: obesity, hypertension, hyperglycemia, hypertriglyceridemia, and low high‐density lipoprotein. Individuals with MetS also typically have elevated plasma levels of the antifibrinolytic factor, plasminogen activator inhibitor‐1 (PAI‐1), but the relationships between PAI‐1 and MetS diagnostic criteria are not clear. Understanding these relationships can elucidate the relevance of MetS to cardiovascular disease risk, because PAI‐1 is associated with ischemic events and directly involved in thrombosis.Methods and ResultsIn a cross‐sectional analysis of 2220 Ghanaian men and women from urban and rural locales, we found the age‐standardized prevalence of MetS to be as high as 21.4% (urban women). PAI‐1 level increased exponentially as the number of diagnostic criteria increased linearly (P<10−13), supporting the conclusion that MetS components have a joint effect that is stronger than their additive contributions. Body mass index, triglycerides, and fasting glucose were more strongly correlated with PAI‐1 than with canonical MetS criteria, and this pattern did not change when pair‐wise correlations were conditioned on all other risk factors, supporting an independent role for PAI‐1 in MetS. Finally, whereas the correlations between conventional risk factors did not vary significantly by sex or across urban and rural environments, correlations with PAI‐1 were generally stronger among urban participants.ConclusionsMetS prevalence in the West African population we studied was comparable to that of the industrialized West. PAI‐1 may serve as a key link between MetS, as currently defined, and the endpoints with which it is associated. Whether this association is generalizable will require follow‐up.

Plasminogen Activator Inhibitor-1 Is a Marker and a Mediator of Senescence

“…Evidence from numerous studies over the last three decades illustrate that PAI-1, beyond its role in fibrinolysis, also regulates numerous pathophysiological processes. These include metabolic syndrome, 16 chronic kidney disease, 17 multi-organ fibrosis 18 and aging. 19 …”

Proteolysis is the most fundamental property of malignancy and its inhibition may be used therapeutically (Review)

“…However, certain types of prostate cancer are aggressive, can spread quickly and exhibit high proteolytic activity ( 28 - 31 ). This is also a case for other types of cancer, such as breast, colon and oral carcinomas among others ( 32 - 36 ).…”

“…Protease nexin can also inhibit tPA and uPA, however, PAI-1 remains a major inhibitor of plasmin-driven proteolysis ( 35 , 70 - 72 ). PAI-1 is overexpressed in various diseases, such as obesity and metabolic syndrome, and has been linked to risk of thrombosis in patients with these conditions ( 36 , 73 , 74 ). Also, it has been reported that a high activity of PAI-1 is associated with recurrent pregnancy loss ( 75 , 76 ).…”

Metabolic Syndrome: Impact of Dietary Therapy

“…Other markers used for diagnosis of metabolic syndrome include high-sensitivity C-reactive protein concentrations (hs-CRP) ≥3 mg/dL [10], uric acid [11], fibrinogen [12], plasminogen activator inhibitor-1 [13,14], increased homocysteine [15,16], and decreased adiponectin [17]. Fibrinogen, plasminogen activator inhibitor-1, cytokines, and hs-CRP protein are often elevated in patients with MetS, resulting in a prothrombotic and pro-inflammatory state.…”