Impaired fibrinolysis in coronary artery disease

Francis, Robert B.; Kawanishi, David T.; Baruch, Terrence; Mahrer, Peter R.; Rahimtoola, Shahbudin H.; Feinstein, Donald I.

doi:10.1016/0002-8703(88)90878-2

Cited by 122 publications

(39 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[7][8][9][10][11] Because PAI-1 is the primary regulator of fibrinolytic activity in vivo, alterations in PAI-1 might be expected to significantly modify the risk of the development of atherosclerosis, with higher levels of PAI-1 resulting in decreased endogenous fibrinolysis favoring the progression of atherosclerosis and low levels providing some degree of protection. Consistent with this hypothesis, a common polymorphism within the PAI-1 promoter that influences PAI-1 gene transcription in vitro has been shown to be associated with the risk of atherosclerosis in several studies, 35,36 although this association is not confirmed in others.…”

Section: Discussionmentioning

confidence: 99%

Atherosclerosis Progression in LDL Receptor–Deficient and Apolipoprotein E–Deficient Mice Is Independent of Genetic Alterations in Plasminogen Activator Inhibitor-1

Sjöland

Eitzman

Gordon

et al. 2000

ATVB

View full text Add to dashboard Cite

Abstract-Impaired fibrinolysis has been linked to atherosclerosis in a number of experimental and clinical studies.Plasminogen activator inhibitor type 1 (PAI-1) is the primary inhibitor of plasminogen activation and has been proposed to promote atherosclerosis by facilitating fibrin deposition within developing lesions. We examined the contribution of PAI-1 to disease progression in 2 established mouse models of atherosclerosis. Mice lacking apolipoprotein E (apoEϪ/Ϫ) and mice lacking the low density lipoprotein receptor (LDLRϪ/Ϫ) were crossbred with transgenic mice overexpressing PAI-1 (resulting in PAI-1 Tg ϩ /apoEϪ/Ϫ and PAI-1 Tg ϩ /LDLRϪ/Ϫ, respectively) or were crossbred with mice completely deficient in PAI-1 gene expression (resulting in PAI-1Ϫ/Ϫ/apoEϪ/Ϫ and PAI-1Ϫ/Ϫ/LDLRϪ/Ϫ, respectively). All animals were placed on a western diet (21% fat and 0.15% cholesterol) at 4 weeks of age and analyzed for the extent of atherosclerosis after an additional 6, 15, or 30 weeks. Intimal and medial areas were determined by computer-assisted morphometric analysis of standardized microscopic sections from the base of the aorta. Atherosclerotic lesions were also characterized by histochemical analyses with the use of markers for smooth muscle cells, macrophages, and fibrin deposition. Typical atherosclerotic lesions were observed in all experimental animals, with greater severity at the later time points and generally more extensive lesions in apoEϪ/Ϫ than in comparable LDLRϪ/Ϫ mice. No significant differences in lesion size or histological appearance were observed among PAI-1Ϫ/Ϫ, PAI-1 Tg ϩ , or PAI-1 wild-type mice at any of the time points on either the apoEϪ/Ϫ or LDLRϪ/Ϫ genetic background. We conclude that genetic modification of PAI-1 expression does not significantly alter the progression of atherosclerosis in either of these well-established mouse models. These results suggest that fibrinolytic balance (as well as the potential contribution of PAI-1 to the regulation of cell migration) plays only a limited role in the pathogenesis of the simple atherosclerotic lesions observed in the mouse. Key Words: atherosclerosis Ⅲ plasminogen activator inhibitor-1 Ⅲ apolipoprotein E Ⅲ low density lipoprotein receptors Ⅲ transgenic mice

show abstract

Section: Discussionmentioning

confidence: 99%

Atherosclerosis Progression in LDL Receptor–Deficient and Apolipoprotein E–Deficient Mice Is Independent of Genetic Alterations in Plasminogen Activator Inhibitor-1

Sjöland

Eitzman

Gordon

et al. 2000

ATVB

View full text Add to dashboard Cite

show abstract

“…A low fibrinolytic potential has been shown to be a marker for increased risk of an adverse coronary event (26,41). This makes fibrinolysis clinically significant to populations at risk for an ischemic event.…”

Section: Introductionmentioning

confidence: 99%

“…tPA is the primary stimulator of fibrinolysis, while PAI-1 is the primary inhibitor. Fibrinolytic activity is stimulated by a number of factors including epinephrine, low blood glucose, shear stress placed on endothelial cells of blood vessels (15) and exercise (8,12,26). Low fibrinolytic potential is associated with an increased risk for an ischemic event (18, 26).…”

Section: Introductionmentioning

confidence: 99%

The effects of whole body vibration and exercise on fibrinolysis in men

Boyle

Nagelkirk

2010

Eur J Appl Physiol

View full text Add to dashboard Cite

“…Low plasma fibrinolytic activity due to increased PAI-1 levels precedes coronary artery disease (Francis et al 1988, Meade et al 1993 and even predicts the occurrence of first acute myocardial infarction (Held et al 1997, Thogersen et al 1998) and reinfarction as well (Hamsten et al 1987). Insulin resistance is associated with higher PAI-1 concentrations and increased PAI-1 has been detected in atheromatous material of patients with type 2 diabetes as compared with non-diabetic patients (Schneiderman et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Plasminogen activator inhibitor-1 promoter activity in adipocytes is not influenced by the 4 G/5 G promoter polymorphism and is regulated by a USF-1/2 binding site immediately preceding the polymorphic region

Zietz

Drobnik

Herfarth

et al. 2004

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with obesity indicating that adipocytes influence PAI-1 plasma levels. In addition, the 4 G/5 G promoter polymorphism of the PAI-1 gene may modulate PAI-1 transcription. We investigated the transcriptional regulation of the human PAI-1 gene in adipocytes and analyzed the genetic contribution of the 4 G/5 G polymorphism. The PAI-1 promoter was analyzed using electrophoretic mobility shift assays (EMSAs) and luciferase reporter gene assays. A putative binding site for the upstream stimulatory factor-1/2 (USF-1/2) at the polymorphic region of the PAI-1 promoter was identified.

show abstract

Impaired fibrinolysis in coronary artery disease

Cited by 122 publications

References 20 publications

Atherosclerosis Progression in LDL Receptor–Deficient and Apolipoprotein E–Deficient Mice Is Independent of Genetic Alterations in Plasminogen Activator Inhibitor-1

Atherosclerosis Progression in LDL Receptor–Deficient and Apolipoprotein E–Deficient Mice Is Independent of Genetic Alterations in Plasminogen Activator Inhibitor-1

The effects of whole body vibration and exercise on fibrinolysis in men

Plasminogen activator inhibitor-1 promoter activity in adipocytes is not influenced by the 4 G/5 G promoter polymorphism and is regulated by a USF-1/2 binding site immediately preceding the polymorphic region

Contact Info

Product

Resources

About