Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk

Abstract

The habitual level of PAI-1 is influenced by many factors, of which obesity and insulin resistance are the most important. It is possible to reduce plasma PAI-1 by changes in life style, e.g. weight reduction and physical activity. Data on potential interactions between environmental and metabolic variables on one hand, and the 4G/5G-polymorphism on the other hand, are still scarce. It becomes more and more clear that PAI-1 may possibly not be a major (causal) factor in cardiovascular disease, but its role in inflammation deserves further attention. In the presence of the 4G-allele not only the PAI-1 response was more pronounced, but also the response of other acute-phase reactants, which implies that the increases of these reactants are secondary to the increase in PAI-1. A myocardial infarction also provokes an acute phase response. It can thus be hypothesized that the 4G-allele might exacerbate tissue injury during the acute phase after a myocardial infarction, and thereby negatively affect the prognosis.

Effects of sulfonylurea treatment on blood plasminogen activator inhibitor-1 levels in patients with type 2 diabetes mellitus: A network meta-analysis

“…In particular, PAI-1 contributes to the determination ofoverall fibrinolytic activity [3] Reportedly, patients with type 2 diabetes mellitus have elevated blood PAI-1 levels and are prone to thrombosis; therefore, a relationship exists between elevated PAI-1 levels, arteriosclerosis, and cardiovascular disease onset [3]. Elevated blood PAI-1levels are caused by tumor necrosis factor-α (TNF-α), oxidative stress, and low-density lipoprotein-type hyperlipoproteinemia andare correlated with insulin resistance, triacylglycerol levels, and very low-density lipoprotein levels [2,[5][6][7]. Thecontrol of these factors is thought to play an important rolein the maintenance of low blood PAI-1 levels.…”

“…Therefore, in patients with type 2 diabetes mellitus,an important treatment goal is the prevention of cardiovascular disease. These patients are also prone to thrombosis, and plasminogen activator inhibitor-1 (PAI-1) levels, which determine fibrinolytic activity in the fibrinolytic system, are considered informative [2]. A previous studyhas reported that elevated blood PAI-1 levels are associated with arteriosclerosis and cardiovascular disease onset [3].…”

Prognostic value of ACE I/D, AT1R A1166C, PAI-I 4G/5G and GPIIIa a1/a2 polymorphisms in myocardial infarction

“…The polymorphism is located in the gene promoter region (chromosome 7) and results in allele-specific responses to multiple agents. Accordingly, studies have shown the 4G allele to be associated with both higher levels of PAI-1 and cardiovascular risk [8].…”

Plasminogen activator inhibitor 1: Mechanisms of its synergistic regulation by growth factors

“…PAI-1 levels are positively correlated with the serum triglyceride levels and hypertension . However, some changes in life style, such as weight reduction and increased physical activity, can decrease plasma PAI-1 activity in affected individuals (Hoekstra, Geleijnse et al 2004).…”