Increased Plasminogen Activator Inhibitor Type 1 in Coronary Artery Atherectomy Specimens From Type 2 Diabetic Compared With Nondiabetic Patients

Sobel, Burton E.; Woodcock‐Mitchell, Janet; Schneider, David J.; Holt, Robert E.; Marutsuka, Kousuke; Gold, Herman K.

doi:10.1161/01.cir.97.22.2213

Cited by 248 publications

(142 citation statements)

References 22 publications

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“…It has been reported that circulating levels of PAI-1 are increased in type 2 diabetic patients (27), and predict myocardial infarction (28,29). The plasma levels of PAI-1 antigen are reported to be increased in subjects with hypertension, dyslipidemia, and hyperinsulinemia (30).…”

Section: Plasma Levels Of Tpa Antigen and Pai-1 Antigenmentioning

confidence: 99%

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

et al. 2005

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Section: Plasma Levels Of Tpa Antigen and Pai-1 Antigenmentioning

confidence: 99%

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

et al. 2005

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“…9,10 Expression of PAI-1 is increased in the vessel wall in patients with diabetes, a group particularly prone to exhibit restenosis. 11,12 In mice and other laboratory animals, increased arterial wall expression of PAI-1 has been found to promote increased neointimal cellularity after vascular injury. [13][14][15] By contrast, the cellular response to exogenous injury was significantly decreased after arterial injury in PAI-1-deficient mice.…”

mentioning

confidence: 99%

Augmentation of Proliferation of Vascular Smooth Muscle Cells by Plasminogen Activator Inhibitor Type 1

Chen

Budd

Kelm

et al. 2006

ATVB

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Objective-Proliferation of vascular smooth muscle cells (VSMCs) contributes to restenosis after coronary intervention.We have shown previously that increased expression of plasminogen activator inhibitor type 1 (PAI-1) limits VSMC apoptosis. Because apoptosis and proliferation appear to be linked, we sought to determine whether increased PAI-1 would affect VSMC proliferation. Methods and Results-VSMCs were explanted from control and transgenic mice (SM22-PAI ϩ ) in which VSMC expression of PAI-1 was increased. Increased growth of SM22-PAI ϩ -VSMCs (2.3Ϯ0.4-fold) reflected, at least partially, increased proliferation. Greater expression of FLICE-like inhibitory protein (FLIP; 2.7-fold) and its cleaved active form were seen in SM22-PAI ϩ -VSMCs. The balance between caspase-8 and FLIP favored proliferation in SM22-PAI ϩ -VSMCs. Increased expression of NF-B and activation of extracellular signal-regulated kinase (ERK) were demonstrated in SM22-PAI ϩ -VSMCs (foldϭNF-Bϭ2.2Ϯ0.1, foldϭphosphorylated-ERKϭ1.6Ϯ0.1). Results were confirmed when expression of PAI-1 was increased by transfection. Inhibition of NF-B and ERK attenuated proliferation in SM22-PAI ϩ -VSMCs. Increased expression of PAI-1 promoted proliferation when VSMCs were exposed to tumor necrosis factor (TNF). Conclusions-Increased expression of PAI-1 is associated with greater activity of FLIP that promotes VSMC proliferation through NF-B and ERK. Thus, when vascular wall expression of PAI-1 is increased, restenosis after coronary intervention is likely to be potentiated by greater proliferation of VSMC and resistance to apoptosis.

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“…Increased PAI-1 has been implicated in both coronary arteries disease and venous thromboembolic events, by promoting plaque formation and venous thrombosis. [2,3,7,8] PAI-1 has also been shown to delay wound healing in vitro mostly through impairing angiogenesis and by inhibiting integrinvitronectin and vitronectin-vitronectin which are essential for cell migration and angiogenesis though activation of vascular endothelial growth factor receptor 2. [9][10][11] Our patient presents with multiple, chronic, non-healing wounds of varying locations and depths.…”

Section: Discussionmentioning

confidence: 99%

4G/4G PAI-1 gene variant in a patient with non-healing ulcers

Peluso

Caffrey

Milner

2015

JER

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Plasminogen activator inhibitor is a serine protease inhibitor from the serpin gene family that modulates fibrin clot breakdown. PAI-1 irreversibly inhibits tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) from activating plasminogen. PAI-1 also inhibits integrin-vitronectin and vitronectin-vitronectin interactions that are essential for cell migration, adhesion, and angiogenesis. We describe a patient, who developed chronic non-healing ulcers after minimal trauma to several areas of his body. Genetic testing revealed the 4G/4G homozygous genotype for the polymorphism in the promoter region of the PAI-1 gene. Increased PAI-1 activity prevents the breakdown of the fibrin clot and cell migration to remodel damaged tissue. A combination of poor clot fibrinolysis and cell recruitment to the site of injury may explain our patient's non-healing ulcers following minor traumatic injury. Early treatment with excision and skin grafting may benefit patients presenting with non-healing ulcers and the homozygous 4G/4G PAI-1 variant. To our knowledge, there have been no reports in the literature associating PAI-1 overexpression and chronic non-healing wounds.

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Increased Plasminogen Activator Inhibitor Type 1 in Coronary Artery Atherectomy Specimens From Type 2 Diabetic Compared With Nondiabetic Patients

Cited by 248 publications

References 22 publications

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

Augmentation of Proliferation of Vascular Smooth Muscle Cells by Plasminogen Activator Inhibitor Type 1

4G/4G PAI-1 gene variant in a patient with non-healing ulcers

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