Aggregating Human Platelets Stimulate the Expression of Thrombin Receptors in Cultured Vascular Smooth Muscle Cells via the Release of Transforming Growth Factor-β
            <sub>1</sub>
            and Platelet-Derived Growth Factor
            <sub>AB</sub>

Schini‐Kerth, Valérie B.; Bassus, S.; Fißlthaler, Beate; Kirchmaier, C. M.; Busse, Rudi

doi:10.1161/01.cir.96.11.3888

Cited by 51 publications

(38 citation statements)

References 57 publications

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“…44 The association between the Pl A1 homozygotes and more stenotic, stable plaques may be the result of genotypic differences in the VSMC proliferation and fibrous tissue generation in the intima after endothelial injury, due to differences in the function of the endothelial/VSMC ␤ 3 integrins, which mediate these responses. 6,10,14,15 This hyperplastic response may be weaker in men with the Pl A2 allele, and thus, the coronary plaques of men with the Pl A2 allele may have thinner fibrous caps, and their plaques may be less stenotic and more prone to rupture. Genotypic differences in thrombosis may also be due to differences in platelet aggregability.…”

Section: Discussionmentioning

confidence: 99%

“…8 -13 ␣ v ␤ 3 integrin is a receptor that mediates different kinds of stimuli to VSMCs, causing their proliferation and subsequent fibrous tissue generation and intimal hyperplasia after injuries. 6,10,14,15 Platelet Pl A polymorphism of the GPIIIa gene is produced by a single point mutation in exon 2 of the GPIIIa gene, leading to substitution of leucine (Pl A1 ) for proline (Pl A2 ) and consequent changes in the protein conformation and spatial orientation of the fibrinogen-binding region. 16 The functional importance of the Pl A polymorphism as an important inherited risk factor for MI was first suggested by Weiss and colleagues.…”

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confidence: 99%

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Glycoprotein IIIa Pl ^A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Mikkelsson

Perola²,

Laippala³

et al. 1999

ATVB

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Abstract-Glycoprotein IIIa (GPIIIa) has a key role in the aggregation of thrombocytes, and it also mediates intimal hyperplasia after endothelial injuries; the possible association of the Pl A1/A2 polymorphism of the gene for GPIIIa with coronary thrombosis and with the progression of coronary artery disease (CAD) is still to be confirmed. Therefore, the association of the Pl A polymorphism with the development of coronary atherosclerosis, coronary narrowing, and myocardial infarction (MI) was studied in a prospective, consecutive autopsy series of 300 middle-aged, white Finnish men (33 to 69 years) suffering sudden out-of-hospital or violent death. Coronary atherosclerosis was measured morphometrically and the coronary stenosis percentage determined from a cast rubber model of the coronary tree. We found a significant inverse relation (Pϭ0.01) between the Pl A2 -positive genotype and coronary artery stenosis. The frequency of possessing the Pl A2 allele was significantly (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.22 to 0.98) lower among men with Ͼ50% coronary stenosis (18.3%) than among those with Ͻ25% stenosis (32.9%). Although the Pl A polymorphism was not directly associated with MI, the Pl A2 allele was present in 11 of the 22 men (50%) with MI and coronary thrombosis (OR 6.6, 95% CI 2.1 to 22.8) but in only 6 of the 47 (12.8%) with MI associated with severe stenosis in the absence of thrombosis. In line with this result, men possessing the Pl A2 allele also had a larger area of fissured and ulcerated complicated lesions in their coronary arteries (PϽ0.05). The present results suggest that the Pl A polymorphism is involved in the development of CAD and MI. Men with the Pl A2 allele may harbor more thin-walled, vulnerable coronary plaques, plaques prone to rupture, leading to massive, fatal thrombosis. In contrast, men homozygous for the Pl A1 allele may more often show stable plaques and present with infarction caused by progressive coronary stenosis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Glycoprotein IIIa Pl ^A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Mikkelsson

Perola²,

Laippala³

et al. 1999

ATVB

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“…Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF-AB) have been shown to induce PAR-1 expression. 12,13 bFGF and cyclic strain applied together increased PAR-1 expression beyond the increase induced by either stimulus alone; whereas PDGF-AB, when applied to cells concomitantly with cyclic strain, had no additional effect on PAR-1 expression.…”

mentioning

confidence: 84%

“…Aggregating platelets have been shown to induce thrombin receptor expression in cultured VSMCs through the release of transforming growth factor-␤1 and PDGF-AB. 13 In vascular cells, the growth-promoting effects of hemodynamic forces increase the release of growth factors, such as PDGF 31 and bFGF, 23 which also enhances the expression of PAR-1. 12 This additive effect of cyclic strain and bFGF on PAR-1 expression (Figure 7) suggests that cyclic strain and bFGF may cooperatively promote mitogenesis of VSMCs in response to thrombin.…”

Section: Nguyen Et Al Cyclic Strain and Par-1 In Smooth Muscle Cellsmentioning

confidence: 99%

Cyclic Strain Increases Protease-Activated Receptor-1 Expression in Vascular Smooth Muscle Cells

et al. 2001

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Abstract-Cyclic strain regulates many vascular smooth muscle cell (VSMC) functions through changing gene expression.This study investigated the effects of cyclic strain on protease-activated receptor-1 (PAR-1) expression in VSMCs and the possible signaling pathways involved, on the basis of the hypothesis that cyclic strain would enhance PAR-1 expression, reflecting increased thrombin activity. Uniaxial cyclic strain (1 Hz, 20%) of cells cultured on elastic membranes induced a 2-fold increase in both PAR-1 mRNA and protein levels. Functional activity of PAR-1, as assessed by cell proliferation in response to thrombin, was also increased by cyclic strain. In addition, treatment of cells with antioxidants or an NADPH oxidase inhibitor blocked strain-induced PAR-1 expression. Preincubation of cells with protein kinase inhibitors (staurosporine or Ro 31-8220) enhanced strain-increased PAR-1 expression, whereas inhibitors of NO synthase, tyrosine kinase, and mitogen-activated protein kinases had no effect. Cyclic strain in the presence of basic fibroblast growth factor induced PAR-1 mRNA levels beyond the effect of cyclic strain alone, whereas no additive effect was observed between cyclic strain and platelet-derived growth factor-AB. Our findings that cyclic strain upregulates PAR-1 mRNA expression but that shear stress downregulates this gene in VSMCs provide an opportunity to elucidate signaling differences by which VSMCs respond to different mechanical forces. (Hypertension. 2001;38: 1038-1043.)

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“…17) Platelet aggregation by injured endothelial cells or by activated platelets due to turbulent flow in the aneurysm is another highly possible factor of activating preserved latent TGFβ 1 . 18) It is known that TGFβ 1 usually inhibits proliferation and migration of smooth muscle cells, but recently it was reported that smooth muscle cells from injured vascular lesions respond to TGFβ 1 differently, and TGFβ 1 stimulates these cells to proliferate and to induce enhanced accumulation of extracellular matrix. 19) This process is reported to be associated with a decreased ratio of type II / type I receptors.…”

Section: Localized Stenosismentioning

confidence: 99%

Remodeling of Coronary Artery Lesions Due to Kawasaki Disease.

Suzuki

Miyagawa‐Tomita²,

Nakazawa³

et al. 2000

Jpn Heart J

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SUMMARYSince the original report of Kawasaki disease in 1967 1) more than 150,000 cases have been reported in Japan.2) Although there have been no nationwide epidemics in Japan since 1987, more than 6,000 newly diagnosed cases are reported every year, and the number has been increasing year by year despite the decreasing birth rate.2,3) The etiology of the disease is still unknown. High dose intravenous gammaglobulin is currently used during the acute phase in 84 % of the patients in Japan with a concomitant decrease in coronary arterial sequelae.1) However, 7-13 % of the patients still have persistent coronary artery aneurysms after the acute stage. 2,3)The aneurysms are seen mostly in the proximal coronary arteries, and are often associated with aneurysms in the distal coronary artery segments ( Figure 1A, 2A). Most of the patients show a decrease in the size of aneurysms soon after the acute phase ( Figure 1B). However, the aneurysms may progress to obstructive lesions even after initial regression ( Figures 1C, D, 2B). 4)Such obstructive lesions may cause sudden death or myocardial infarction. Long term follow-up of coronary artery lesions has revealed several characteristic features, including progressive localized stenosis ( Figure 1D), extensive recanalizations ( Figure 2D) and development of collateral arteries. [4][5][6] Progressive increases in aneurysm size and the appearance of new aneurysms in the late phase have also been reported.The basic mechanisms of the coronary arterial remodeling in Kawasaki disease have not yet been elucidated. Only recently has immunohistochemical staining in formalinfixed specimens become feasible.7) This is a major technical breakthrough since it is almost impossible to obtain fresh frozen specimens of coronary artery lesions of Kawasaki disease. 8)In this paper, we compare immunohistochemical findings in coronary artery lesions with the corresponding coronary angiographic findings, and attempt to make inferences as to the mechanism of remodeling both in early and late phases of the disease based on the expression of vascular growth factors. 8) (Jpn Heart J 2000; 41: 245-256)

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Aggregating Human Platelets Stimulate the Expression of Thrombin Receptors in Cultured Vascular Smooth Muscle Cells via the Release of Transforming Growth Factor-β ₁ and Platelet-Derived Growth Factor _AB

Cited by 51 publications

References 57 publications

Glycoprotein IIIa Pl ^A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Glycoprotein IIIa Pl ^A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Cyclic Strain Increases Protease-Activated Receptor-1 Expression in Vascular Smooth Muscle Cells

Remodeling of Coronary Artery Lesions Due to Kawasaki Disease.

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Aggregating Human Platelets Stimulate the Expression of Thrombin Receptors in Cultured Vascular Smooth Muscle Cells via the Release of Transforming Growth Factor-β 1 and Platelet-Derived Growth Factor AB

Cited by 51 publications

References 57 publications

Glycoprotein IIIa Pl A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Glycoprotein IIIa Pl A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Cyclic Strain Increases Protease-Activated Receptor-1 Expression in Vascular Smooth Muscle Cells

Remodeling of Coronary Artery Lesions Due to Kawasaki Disease.

Contact Info

Product

Resources

About

Aggregating Human Platelets Stimulate the Expression of Thrombin Receptors in Cultured Vascular Smooth Muscle Cells via the Release of Transforming Growth Factor-β ₁ and Platelet-Derived Growth Factor _AB

Glycoprotein IIIa Pl ^A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Glycoprotein IIIa Pl ^A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly