Limits...
Functional stability of plasminogen activator inhibitor-1.

Yasar Yildiz S, Kuru P, Toksoy Oner E, Agirbasli M - ScientificWorldJournal (2014)

Bottom Line: The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate.Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure.This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey.

ABSTRACT
Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.

Show MeSH

Related in: MedlinePlus

Role of PAI-1 in fibrinolytic system.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4214104&req=5

fig1: Role of PAI-1 in fibrinolytic system.

Mentions: Lysis of fibrin in a blood clot and pericellular proteolysis are the results of activation of plasminogen by t-PA and u-PA, respectively. As potential check points in the regulation of fibrinolysis, the activity of plasmin can be directly inhibited by α2-antiplasmin or thrombin activatable fibrinolysis inhibitor (TAFI) or plasminogen activator inhibitors can block the conversion of plasminogen to plasmin [4]. PAI-1 is the most important direct physiological inhibitor of t-PA and u-PA and major regulator of the fibrinolytic system (Figure 1) [5]. Severity and unfavorable outcomes were reported in a number of diseases due to elevated plasma levels of PAI-1 antigen [6–9] and activity [9–11]; as a result, PAI-1 is considered as a biomarker and potential molecular target for therapeutics.


Functional stability of plasminogen activator inhibitor-1.

Yasar Yildiz S, Kuru P, Toksoy Oner E, Agirbasli M - ScientificWorldJournal (2014)

Role of PAI-1 in fibrinolytic system.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4214104&req=5

fig1: Role of PAI-1 in fibrinolytic system.
Mentions: Lysis of fibrin in a blood clot and pericellular proteolysis are the results of activation of plasminogen by t-PA and u-PA, respectively. As potential check points in the regulation of fibrinolysis, the activity of plasmin can be directly inhibited by α2-antiplasmin or thrombin activatable fibrinolysis inhibitor (TAFI) or plasminogen activator inhibitors can block the conversion of plasminogen to plasmin [4]. PAI-1 is the most important direct physiological inhibitor of t-PA and u-PA and major regulator of the fibrinolytic system (Figure 1) [5]. Severity and unfavorable outcomes were reported in a number of diseases due to elevated plasma levels of PAI-1 antigen [6–9] and activity [9–11]; as a result, PAI-1 is considered as a biomarker and potential molecular target for therapeutics.

Bottom Line: The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate.Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure.This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey.

ABSTRACT
Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.

Show MeSH
Related in: MedlinePlus