Natriuretic Factors and Nitric Oxide Suppress Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells

Bouchie, Julie L.; Hansen, Holger C.; Feener, Edward P.

doi:10.1161/01.atv.18.11.1771

Cited by 105 publications

(95 citation statements)

References 69 publications

(77 reference statements)

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“…If eNOS expression or activity is increased in PAI-1 Ϫ/Ϫ mice, this might protect these animals from the effects of L-NAME. There is experimental evidence that NO in fact regulates PAI-1 production, 9 whereas we are not aware of any evidence supporting the converse. Furthermore, basal systolic blood pressure is similar in WT and PAI-1 Ϫ/Ϫ mice, suggesting that a major alteration in vascular NO production is unlikely to exist in the setting of PAI-1 deficiency.…”

Section: Discussionmentioning

confidence: 68%

“…29 Our group and others have shown that angiotensin II regulates PAI-1 expression in vitro and in vivo, 16,30 -33 and NO suppresses PAI-1 expression after stimulation by angiotensin II in aortic smooth muscle cells. 9 Together, these factors would be anticipated to increase vascular PAI-1 production during treatment with L-NAME. Indeed, it was recently shown that arterial PAI-1 expression increases 4-fold in L-NAME-treated rats, which can be prevented by ACE inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…6,8 Aside from the well-defined roles that endothelial NO plays in regulating vascular tone and structure, it has also been reported that NO suppresses plasminogen activator inhibitor-1 (PAI-1) expression in vascular tissue. 9 It was recently reported that long-term NOS inhibition induced vascular PAI-1 expression in rat models. 10 PAI-1, a member of the serpin superfamily of serine protease inhibitors, serves as the primary physiological inhibitor of plasminogen activation.…”

mentioning

confidence: 98%

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Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

et al. 2001

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Background-Long-term inhibition of nitric oxide synthase (NOS) is known to induce hypertension and perivascular fibrosis. Recent evidence also suggests that long-term NOS inhibition induces expression of plasminogen activator inhibitor-1 (PAI-1) in vascular tissues and that PAI-1 may contribute to the development of fibrosis after chemical or ionizing injury. On the basis of these observations, we hypothesized that PAI-1 may influence the vascular response to long-term NOS inhibition by N -nitro-L-arginine methyl ester (L-NAME). Methods and Results-We compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis in PAI-1-deficient (PAI-1 Ϫ/Ϫ ) and wild-type (WT) male mice (Nϭ6 per group). At baseline, there were no significant differences in blood pressure between groups. After initiation of L-NAME, systolic blood pressure increased in both groups at 2 weeks. Over an 8-week study period, systolic blood pressure increased to 141Ϯ3 mm Hg in WT animals versus 112Ϯ4 mm Hg in PAI-1 Ϫ/Ϫ mice (PϽ0.0001). The extent of coronary perivascular fibrosis increased significantly in L-NAME-treated WT mice (PϽ0.01 versus PAI-1 Ϫ/Ϫ mice). Cardiac type I collagen mRNA expression was greater in control (PϽ0.01) and L-NAME-treated PAI-1 Ϫ/Ϫ (PϽ0.05) groups than in control WT mice, indicating that PAI-1 deficiency prevents the increase of collagen deposition by promoting matrix degradation. Conclusions-These findings suggest that PAI-1 deficiency alone is sufficient to protect against the structural vascular changes that accompany hypertension in the setting of long-term NOS inhibition. Direct inhibition of vascular PAI-1 activity may provide a new therapeutic strategy for the prevention of arteriosclerotic cardiovascular disease.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

et al. 2001

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“…An increase in PAI-1 attributable to a loss of NO · at these sites may also contribute to lesion formation. 10,11 Some of the PAI-1 expressed and released by endothelial cells remains associated with the cell surface. It can reduce endothelial fibrinolytic activity, thus promoting local thrombus formation.…”

Section: Discussionmentioning

confidence: 99%

“…9 The antithrombotic effects of NO · on arterial endothelium are also attributable to inhibition of the expression of the prothrombotic protein plasminogen activator inhibitor-1 (PAI-1). 10,11 Nitric oxide is synthesized by nitric oxide synthase (NOS), which is present in large concentrations in the endothelium. In the endothelium, it has been shown that NOS expression is regulated by flowmediated shear stress and is downregulated at sites with low flow.…”

Section: See P 2764mentioning

confidence: 99%

Downregulation of Endocardial Nitric Oxide Synthase Expression and Nitric Oxide Production in Atrial Fibrillation

et al. 2002

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Background— In the arterial endothelium, laminar flow and cyclical stretch induce expression of NO synthase (NOS). We hypothesized that atrial fibrillation (AF) causes a downregulation of atrial endocardial NOS expression and NO · production. Because NO · has antithrombotic properties, this may contribute to thromboembolism in AF. Methods and Results— In pigs, AF was produced with rapid atrial pacing at 600 bpm for 1 week, whereas controls had atrial pacing at 100 bpm. All animals had catheter ablation of the AV junction and ventricular pacing at 100 bpm. NO · production from freshly isolated tissue was measured by a NO · -specific microelectrode. Left atrial basal and stimulated NO · production was decreased in AF by 73% and 71% ( P <0.01). Endocardial NOS expression, determined by Western analysis, was also significantly decreased by 46%. Expression of the prothombotic protein plasminogen activator inhibitor 1 (PAI-1) is known to be regulated by NO · and was increased in the left atrium by 1.8-fold in AF ( P <0.05). NO · concentration was decreased in the left atrial appendage, although NOS expression was not affected. Neither NOS concentration, NO · levels, nor PAI-1 expression were altered in the aortas or right atria of animals with AF. Conclusions— AF is associated with a marked decrease in endocardial NOS expression and NO · bioavailability and an increase in PAI-1 expression in the left atrium. These data suggest that organized atrial contraction is needed to maintain normal endocardial expression of NOS. It is likely that loss of this antithrombotic enzyme contributes to the thromboembolic phenomena commonly observed in AF.

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Angiotensin-Converting Enzyme Inhibitor Prevents Plasminogen Activator Inhibitor-1 Expression in a Rat Model with Cardiovascular Remodeling Induced by Chronic Inhibition of Nitric Oxide Synthesis

Katoh¹,

Egashira²,

Mitsui³

et al. 2000

Journal of Molecular and Cellular Cardiology

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Natriuretic Factors and Nitric Oxide Suppress Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells

Cited by 105 publications

References 69 publications

Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

Downregulation of Endocardial Nitric Oxide Synthase Expression and Nitric Oxide Production in Atrial Fibrillation

Angiotensin-Converting Enzyme Inhibitor Prevents Plasminogen Activator Inhibitor-1 Expression in a Rat Model with Cardiovascular Remodeling Induced by Chronic Inhibition of Nitric Oxide Synthesis

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