Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis

Giezen, J.J.J. van; Brakkee, J. G. P.; Dreteler, G.H.; Bouma, Bonno N.; Jansen, J.W.C.M.

doi:10.1097/00001721-199404000-00015

Cited by 57 publications

(42 citation statements)

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“…A RARE was identified at position − 1659. This element is responsible for RA potentiation of the PMA-mediated induction of PAI-2 in human myeloid leukemia cells [329]. The PAI-2 RARE is composed of a GRE half-site separated by seven bases from a RARE half-site.…”

Section: The Pai-2 Genementioning

confidence: 99%

The plasminogen activator system: biology and regulation

Irigoyen

Muñoz‐Cánoves²,

Montero

et al. 1999

CMLS, Cell. Mol. Life Sci.

348

271

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The regulation of plasminogen activation involves genes for two plasminogen activators (tissue type and urokinase type), two specific inhibitors (type 1 and type 2), and a membrane-anchored urokinase-type plasminogen-activator-specific receptor. This system plays an important role in various biological processes involving extracellular proteolysis. Recent studies have revealed that the system, through interplay with integrins and the extracellular matrix protein vitronectin, is also involved in the regulation of cell migration and proliferation in a manner independent of proteolytic activity. The genes are expressed in many different cell types and their expression is under the control of diverse extracellular signals. Gene expression reflects the levels of the corresponding mRNA, which should be the net result of synthesis and degradation. Thus, modulation of mRNA stability is an important factor in overall regulation. This review summarizes current understanding of the biology and regulation of genes involved in plasminogen activation at different levels.

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Section: The Pai-2 Genementioning

confidence: 99%

The plasminogen activator system: biology and regulation

Irigoyen

Muñoz‐Cánoves²,

Montero

et al. 1999

CMLS, Cell. Mol. Life Sci.

348

271

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“…Dexamethasone, a synthetic glucocorticoid, and androgens increase t-PA synthesis in vitro (3)(4)(5) and in vivo (6,7). The level of t-PA expression in breast carcinoma cells correlates with the endogenous level of progesterone receptor (8), and progesterone induces t-PA-related antigen secretion in primary human endometrial cells (9).…”

mentioning

confidence: 99%

Identification of a Multihormone Responsive Enhancer Far Upstream from the Human Tissue-type Plasminogen Activator Gene

Bulens

Merchiers²,

Ibañez–Tallon³

et al. 1997

Journal of Biological Chemistry

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A 2.4-kilobase (kb) DNA fragment, located 7.1 kb upstream from the human tissue-type plasminogen activator (t-PA) gene (t-PA2.4), acts as an enhancer which is activated by glucocorticoids, progesterone, androgens, and mineralocorticoids. Transient expression of t-PAchloramphenicol acetyltransferase reporter constructs in HT1080 human fibrosarcoma cells identified a glucocorticoid responsive unit with four functional binding sites for the glucocorticoid receptor, located between bp ؊7,501 and ؊7,974. The region from bp ؊7,145 to ؊9,578 (t-PA2.4) was found to confer a cooperative induction by dexamethasone and all-trans-retinoic acid (RA) to its homologous and a heterologous promoter, irrespective of its orientation. The minimal enhancer, defined by progressive deletion analysis, comprised the region from ؊7.1 to ؊8.0 kb (t-PA0.9) and encompassed the glucocorticoid responsive unit and the previously identified RA-responsive element located at ؊7. Vascular patency is the result of a dynamic equilibrium between blood coagulation and fibrinolysis. Injury of the vessel wall can initiate the blood clotting cascade resulting in the formation of a hemostatic clot. To counterbalance fibrin deposition, blood contains the fibrinolytic system, one main function of which is to dissolve blood clots in the circulation. It is composed of the inactive precursor plasminogen, which can be converted into the proteolytic enzyme plasmin by the plasminogen activators (PAs) 1 tissue-type and urokinase-type PA (t-PA and u-PA, respectively) leading to the degradation of fibrin. Fibrinolytic activity can be inhibited both at the level of the PAs and plasmin by PA inhibitors (PAI-1 and -2) and ␣ 2 -antiplasmin, respectively (for a review, see ref. 1). Phenotypic analysis of mice deficient for either t-PA, u-PA, or both suggested that t-PA and u-PA were complementary, not only in the prevention of uncontrolled fibrin deposition in vivo but also in distinct processes which require local extracellular proteolytic activity, such as wound healing and gonadotropin-induced ovulation, as reviewed elsewhere (2).Dexamethasone, a synthetic glucocorticoid, and androgens increase t-PA synthesis in vitro (3-5) and in vivo (6, 7). The level of t-PA expression in breast carcinoma cells correlates with the endogenous level of progesterone receptor (8), and progesterone induces t-PA-related antigen secretion in primary human endometrial cells (9). Vitamin A, retinoic acid (RA), and some of its (synthetic) analogues induce t-PA-related antigen secretion by human umbilical vein endothelial cells in vitro (10 -12) and in the plasma as well as in specific tissues of vitamin A-deficient rats in vivo (11,13,14), suggesting that circulating RA might regulate t-PA expression in the vessel wall. The induction of t-PA expression by glucocorticoids and RA can be reproduced in HT1080 human fibrosarcoma cells, and interestingly, both agents induce t-PA mRNA steady state levels and t-PA-related antigen secretion in a cooperative manner.2 Both steroid hormones and RA are t...

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“…Platelet function, which plays a vital role in primary haemostasis, is much less clear in this context. Most reports so far have investigated the effect of synthetic steroids on platelet count, while there are far fewer in which platelet function was analysed, and these were predominantly performed in veterinary research [16,18]. Moreover, until now, the majority of studies have investigated the influence of exogenous steroids on platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

“…So far, few reports have been published on the effect of corticosteroids on platelet function, most of them were veterinary medicine studies [16,18], and their results indicate a suppressive effect of exogenous glucocorticosteroids on blood platelet aggregation in animals [16,19]. These observations contrast with reports on megakaryocyte function in Cushing's disease (CD) patients.…”

Section: Introductionmentioning

confidence: 96%

Ocena funkcji płytek krwi u pacjentów z endogenną hiperkortyzolemią

Świątkowska−Stodulska

Mital

Wiśniewski

et al. 2015

Endokrynologia Polska

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Introduction: It is commonly known that glucocorticoids exert a significant effect on haemostasis. Studies that have analysed the plasmatic coagulation system and fibrinolysis parameters in hypercortisolaemic patients are abundant. Platelet function, which plays a vital role in primary haemostasis, is much less clear in this context. We aimed at assessing platelet function in endogenous hypercortisolaemic patients. Material and methods: Twenty-five hypercortisolaemic patients were included in the study. Twelve of them were diagnosed with overt Cushing's syndrome (OCS) and 13 had subclinical Cushing's syndrome (SCS). Thirty healthy volunteers comprised the control group. In all subjects platelet function parameters were examined: ADP-and collagen-induced platelet aggregation (ADP-IPA and Col-IPA, respectively), IMPACT R (expressed as percentage of surface covered (SC) by platelets and average size (AS) of the adhering particles in μm

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Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis

Cited by 57 publications

References 0 publications

The plasminogen activator system: biology and regulation

The plasminogen activator system: biology and regulation

Identification of a Multihormone Responsive Enhancer Far Upstream from the Human Tissue-type Plasminogen Activator Gene

Ocena funkcji płytek krwi u pacjentów z endogenną hiperkortyzolemią

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