Angiotensin II increases plasminogen activator inhibitor type 1 and tissue-type plasminogen activator messenger RNA in cultured rat aortic smooth muscle cells.

Leeuwen, R.T.J. van; Kol, Amir; Andreotti, Felicita; Kluft, C.; Maseri, Attilio; Sperti, G.

doi:10.1161/01.cir.90.1.362

Cited by 158 publications

(87 citation statements)

References 49 publications

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“…Previous reports have shown that the vasopressive peptide Ang II is a potent stimulator of PAI-1 expression in both vascular endothelial and SMCs 23,24,51 and that angiotensinconverting enzyme (ACE) inhibition reduces both vascular and plasma PAI-1 levels. 18,52 These reports suggest that the renin-angiotensin system, via the actions of Ang II, can contribute to the expression of PAI-1.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24] Control cells and cells pretreated with natriuretic factors for 5 minutes were stimulated with either Ang II or PDGF for 3 hours. Northern blot analyses of both PAI-1 and acidic ribosomal phosphoprotein PO mRNA (36B4, a constitutively expressed mRNA) were performed as described previously.…”

Section: Effect Of Natriuretic Peptides On Pai-1 Mrna Expression In Rmentioning

confidence: 99%

“…[22][23][24][25][26] However, although the processes that upregulate PAI-1 expression have received considerable attention, much less is known regarding the factors and mechanisms that may negatively regulate PAI-1 expression in vascular cells. In this report, we have examined the effect of 2 types of vasorelaxant compounds, natriuretic factors and nitric oxide, on the regulation of PAI-1 expression in VSMCs.…”

mentioning

confidence: 99%

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

Bouchie

Hansen

Feener

1998

ATVB

105

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Abstract-Increased expression of plasminogen activator inhibitor-1 (PAI-1) has been reported in atherosclerotic and balloon-injured vessels. Little is known regarding the factors and mechanisms that may negatively regulate PAI-1 expression. In this report, the effect of cGMP-coupled vasoactive hormones, including natriuretic factors and nitric oxide, on the regulation of PAI-1 expression in vascular smooth muscle cells was examined. Atrial natriuretic factor 1-28 (ANF) and C-type natriuretic factor-22 (CNP) reduced angiotensin II (Ang II)-and platelet-derived growth factor-stimulated PAI-1 mRNA expression in rat aortic smooth muscle cells by 50% to 70%, with corresponding reductions in PAI-1 protein release. Treatment of human aortic smooth muscle cells with CNP similarly inhibited both platelet-derived growth factor-induced PAI-1 mRNA expression and PAI-1 protein release by 50%. Dose-response studies revealed that the inhibitory effects of CNP and ANF on PAI-1 expression were concentration dependent, with IC 50 s of Ϸ1 nmol/L for both natriuretic peptides. Ang II-stimulated PAI-1 expression was also inhibited by the nitric oxide donor S-nitroso-N-acetylpenicillamine.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Natriuretic Peptides On Pai-1 Mrna Expression In Rmentioning

confidence: 99%

mentioning

confidence: 99%

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

Bouchie

Hansen

Feener

1998

ATVB

105

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“…112 Conflicting data suggest that losartan may mediate antifibrinolytic activity via reduction of PAI-1 expression and activity, 113-117 and other reports suggest that losartan may inhibit fibrinolysis by alternate actions through prevention of platelet aggregation (Figure 3). 118,119 The different observations about PAI-1 activity and expression may reflect the manner in which the analyses were conducted, such as timing of sample collection and duration of treatment, u3 Reduction of PAI-1 levels by candesartan, valsartan, and irbesartan would, however, suggest that All-mediated inhibition of fibrinolysis may be affected by the AT 1 receptor.…”

Section: Thrombosismentioning

confidence: 98%

Review of the molecular pharmacology of Losartan and its possible relevance to stroke prevention in patients with hypertension

Dı́ez

2006

Clinical Therapeutics

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Background: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study found that a losartan-based regimen, compared with an atenololbased regimen, resulted in a significantly lower risk of stroke in hypertensive patients with left ventricular hypertrophy, despite similar reductions in blood pressure.Objective: The purpose of this review was to examine the molecular and pharmacologic mechanisms that may be associated with the different outcomes observed in the LIFE study.Methods: A PubMed/MEDLINE search of Englishlanguage articles (1990( to February 2006 Results: Losartan's significant effect on stroke may be related to several possible mechanisms that are independent of blood-pressure reductions. These include improvements in endothelial function and vascular structure; decreases in vascular oxidative stress; reductions in left ventricular hypertrophy, reductions in myocardial fibrosis, or both; and modulation of atherosclerotic disease progression. Although some of these effects may be shared by other angiotensin II receptor antagonists (AliAs), and perhaps other antihypertensive classes (eg, angiotensin-converting enzyme inhibitors), the ability of losartan to lower serum uric acid levels--a proposed independent risk factor for cardiovascular disease--appears to be a molecule-specific effect. Alternative explanations of the results of the LIFE study have also been hypothesized, including inappropriate choice of atenolol as an active comparator and differences in central pulse pressures between study groups.Conclusions: This review of the literature suggests that losartan (and perhaps other AliAs) may possess a number of properties, independent of its antihypertensive effects, that may be associated with decreased vulnerability of the plaque, myocardium, and blood.

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“…Although mean cortisol concentration was higher during low salt intake than during high salt intake and serum cortisol concentration increased with the number of PAI-1 4G alleles under high-salt conditions, there was no correlation between cortisol and PAI-1 antigen under either low-or high-salt conditions. Both Ang II (or its hexapeptide metabolite, Ang IV) and aldosterone increase PAI-1 expression in a variety of cell types, including astrocytes, 35 endothelial cells, 4 vascular smooth muscle cells, 36 proximal tubular epithelial cells, 37 and mesangial cells. 38 Systemic infusion of Ang II increases vascular, renal, and hepatic PAI-1 expression in rats, 39 whereas treatment of animals with ACE inhibitors, AT 1 receptor antagonists, or aldosterone receptor antagonists decreases tissue PAI-1 expression.…”

Section: Discussionmentioning

confidence: 99%

Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen

Brown

Murphey²,

Srikuma³

et al. 2001

ATVB

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Abstract-Activation of the renin-angiotensin-aldosterone system (RAAS) is associated with increased circulating PAI-1 antigen and increased risk of thrombotic cardiovascular events. A 4G/5G polymorphism located 675 bp upstream from the transcription start site of the PAI-1 gene affects PAI-1 antigen concentrations. To test the hypothesis that PAI-1 4G/5G genotype influences the effect of activation of the RAAS on PAI-1 expression, we measured morning PAI-1 antigen concentrations in 76 subjects with essential hypertension during low (10 mmol/d) and high (200 mmol/d) salt intake. Low salt intake was associated with activation of the RAAS as measured by plasma renin activity (2.3Ϯ0.2 versus 0.5Ϯ0.0 ng angiotensin I · mL Ϫ1 · h Ϫ1 , PϽ0.001) and aldosterone (529Ϯ40 versus 145Ϯ12 pmol/L). PAI-1 antigen concentrations were 17.9Ϯ2.7, 19.2Ϯ2.5, and 27.8Ϯ4.0 ng/mL during high salt intake and 19.2Ϯ2.7, 21.6Ϯ2.9, and 38.9Ϯ7.2 ng/mL during low salt intake in the 5G/5G (nϭ14), 4G/5G (nϭ40), and 4G/4G (nϭ22) groups, respectively. There was a significant effect of both salt intake (Fϭ6.0, Pϭ0.017) and PAI-1 4G/5G genotype (Fϭ7.6, Pϭ0.001) on PAI-1 antigen. More importantly, there was a significant interactive effect (Fϭ7.8, Pϭ0.001) of salt intake and PAI-1 4G/5G genotype on PAI-1 antigen. PAI-1 4G/5G genotype influenced the relationship between serum triglycerides and PAI-1 antigen such that the relationship was significant only in 4G homozygotes during either high (R 2 ϭ0.31, Pϭ0.014) or low (R 2 ϭ0.37, Pϭ0.006) salt intake. This study identifies an important gene-by-environment interaction that may influence cardiovascular morbidity and the response to pharmacological therapies that interrupt the RAAS. Key Words: thrombosis Ⅲ genetics Ⅲ fibrinolysis Ⅲ coagulation A ctivation of the renin-angiotensin-aldosterone (RAAS) system has been associated with an increased risk of myocardial infarction (MI) and stroke in patients with essential hypertension. 1,2 Conversely, interruption of the RAAS by ACE inhibition reduces the risk of MI in patients at risk for coronary artery disease. 3 Recent studies suggest that the effects of activation and interruption of the RAAS on cardiovascular morbidity and mortality derive in part from an interaction of the RAAS and fibrinolytic systems. 4,5 Endogenous fibrinolysis plays a critical role in limiting thrombosis and depends on the balance between plasminogen activators (primarily tissue plasminogen activator, tPA) and plasminogen activator inhibitors (PAI, predominantly PAI-1). 6,7 Both of these essential fibrinolytic components are synthesized locally in the vascular wall (in endothelial and smooth muscle cells), have short half-lives, and circulate in trace concentrations in the plasma. Increased PAI-1 expression has been demonstrated in atherosclerotic lesions. 8,9 Elevated PAI-1 concentrations are seen in youthful survivors of acute MI compared with age-matched control subjects, 10 and elevated levels of PAI-1 appear to be a risk factor for recurrent MI. 11 PAI-1 antigen and activity are ...

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Angiotensin II increases plasminogen activator inhibitor type 1 and tissue-type plasminogen activator messenger RNA in cultured rat aortic smooth muscle cells.

Cited by 158 publications

References 49 publications

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

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

Review of the molecular pharmacology of Losartan and its possible relevance to stroke prevention in patients with hypertension

Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen

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