BAS/BSCR13 Increased plasminogen activator inhibitor-1 may explain dexamethasone-induced thrombosis as site of intraluminal wire injury

Low, L.; Seckl, J. R.; Walker, B. R.; Hadoke, P. W. F.
September 2010
Heart;Sep2010, Vol. 96 Issue 17, pe16
Academic Journal
We have previously shown that high-dose glucocorticoid treatment reduces neointimal proliferation following arterial injury in mice, but is associated with increased local thrombosis. Clinically, glucocorticoid excess, either in Cushing's syndrome or with chronic treatment, is associated with increased coagulation and decreased fibrinolysis. The few animal (rat) studies which have investigated these effects support the conclusion that glucocorticoid treatment reduces fibrinolysis. This study aimed to determine the influence of glucocorticoid administration on the thrombotic potential in mice. Male C57Bl/6J mice (aged 10-12 weeks) received either vehicle or dexamethasone (dex; 0.1 or 0.8 mg/kg/day) orally for 5 weeks (n=8/group). Tail tip bleeding time was reduced by high-dose dex (52.9±5.6 s) compared with vehicle (87.1±13.6 s; p<0.05). High-dose dex increased plasminogen activator inhibitor-1 (PAI-1; 139.5±15.1% vs vehicle 100.0±10.7%; p<0.05 and decreased tissue plasminogen activator (tPA; 55.9±4.9% vs vehicle 100.0±10.3%; p<0.05) mRNA levels in the heart. In addition, high-dose dex increased total PAI-1 (3.53±0.59 ng/ml vs vehicle 0.96±0.17 ng/ml; p<0.001) and active PAI-1 (0.92±0.09 ng/ml vs vehicle 0.31±0.07 ng/ml; p<0.001) plasma antigen levels. High-dose dex did not alter platelet activation as measured by p-selectin expression using flow cytometry. Low-dose dex had no effect on any parameters described. Dexamethasone-induced thrombosis at the site of intraluminal wire injury may be attributable to alterations in the endogenous fibrinolytic system rather than changes in platelet activity. These results suggest that beneficial inhibition of neointimal proliferation mediated by systemic glucocorticoid administration is negated in part by changes in fibrinolysis leading to large, semi-occlusive thrombi formation at the site of injury.


Related Articles

  • Incretin Receptors for Glucagon-Like Peptide 1 and Glucose-Dependent Insulinotropic Polypeptide Are Essential for the Sustained Metabolic Actions of Vildagliptin in Mice. Flock, Grace; Baggio, Laurie L.; Longuet, Christine; Drucker, Daniel J. // Diabetes;Dec2007, Vol. 56 Issue 12, p3006 

    OBJECTIVE--Dipeptidyl peptidase-4 (DPP4) inhibitors lower blood glucose in diabetic subjects; however, the mechanism of action through which these agents improve glucose homeostasis remains incompletely understood. Although glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic...

  • SELENIUM INTAKE AFFECTS MRNA LEVELS FOR KEY MEDIATORS OF CD4[sup+] T CELL ACTIVATION.  // Ethnicity & Disease;Summer2009 Supplement 3, Vol. 19 Issue 3, p67 

    Levels of selenium (Se) intake have been shown to modulate I cell responses in both humans and animal models. The mechanisms by which Se levels influence these responses remain unclear. The goal of the study was to evaluate the affect of dietary Se levels on the activation of CD4[sup+] T cell...

  • Upregulation of ADAM8 in the Airways of Mice with Allergic Bronchial Asthma. Chiba, Yoshihiko; Onoda, Satoshi; Hattori, Yoshiyuki; Maitani, Yoshie; Sakai, Hiroyasu; Misawa, Miwa // Lung;May/Jun2009, Vol. 187 Issue 3, p179 

    Recent microarray analyses revealed that a disintegrin and metalloproteinase (ADAM) 8 (ADAM8; also called CD156) is one of the asthma candidate genes. However, the function of ADAM8 and its localization in the airways are still poorly understood. In the present study, the changes in the...

  • 15-Deoxy-Δ12,14 Prostaglandin J2 Reduces the Formation of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice. Seno, Takahiro; Hamaguchi, Masahide; Ashihara, Eishi; Kohno, Masataka; Ishino, Hidetaka; Yamamoto, Aihiro; Kadoya, Masatoshi; Nakamura, Kaoru; Murakami, Ken; Matoba, Satoaki; Maekawa, Taira; Kawahito, Yutaka // PLoS ONE;2011, Vol. 6 Issue 10, p1 

    Aim: 15-Deoxy-Δ12,14 Prostaglandin J2 (15d-PGJ2) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ2 can also regulate the expression of inflammatory...

  • Effects of lipopolysaccharides from various Porphyromonas on the expression of CD14 and TLRs in mouse osteoblast. Jia Ge; Xue Ming; Li Ren; LV You; Qiu Li-Hong // Shanghai Journal of Stomatology;Dec2011, Vol. 20 Issue 6, p598 

    PURPOSE: To observe the effect of lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) and Porphyromonas gingivals(P.g) on the expression of CD14 and TLRs in osteoblast. METHODS: MC3T3-E1 cells were stimulated with 10µg/mL P.e-LPS and P.g-LPS. The change of CD14/TLR2 and...

  • Type 1 Diabetes Prone NOD Mice Have Diminished Cxcr1 mRNA Expression in Polymorphonuclear Neutrophils and CD4+ T Lymphocytes. Haurogné, Karine; Pavlovic, Marija; Rogniaux, Hélène; Bach, Jean-Marie; Lieubeau, Blandine // PLoS ONE;7/31/2015, Vol. 10 Issue 7, p1 

    In humans, CXCR1 and CXCR2 are two homologous proteins that bind ELR+ chemokines. Both receptors play fundamental roles in neutrophil functions such as migration and reactive oxygen species production. Mouse Cxcr1 and Cxcr2 genes are located in an insulin-dependent diabetes genetic...

  • sHLA-G expression: is it really worth measuring? Sher, G.; Keskintepe, L.; Ginsburg, M. // Reproductive BioMedicine Online (Reproductive Healthcare Limited;Jan2007, Vol. 14 Issue 1, p9 

    HLA-G is believed to play a pivotal role in the immunoprotection of the semiallogenic embryo. Its expression during pre- and early implantation is correlated with the cleavage rate of the embryo. Studies in congenic mice have revealed that mRNA of both the maternal and paternal haplotypes are...

  • Gene expression profiles of the collecting duct in the mouse renal inner medulla. Takenaka, Masaru; Imai, Enyu; Nagasawa, Yasuyuki; Matsuoka, Yasuko; Moriyama, Toshiki; Kaneko, Tetsuya; Hori, Masatsugu; Kawamoto, Shoko; Okubo, Kousaku // Kidney International;Jan2000, Vol. 57 Issue 1, p19 

    Examines the gene expression responses of the inner renal medullary collecting ducts of mice. Induction of the renal expression of messenger RNA; Identification of another member of the glutathione-S-transferase; Anatomical division of the nephron.

  • Posttranscriptional Regulatory Elements Enhance Antigen Expression and DNA Vaccine Efficacy. Jing Sun; Dingfeng Li; Yanling Hao; Yuwei Zhang; Wenling Fan; Jingjing Fu; Yunzhang Hu; Yong Liu; Yiming Shao // DNA & Cell Biology;May2009, Vol. 28 Issue 5, p233 

    In higher eukaryotes, introns are usually required for efficient pre-mRNA processing. However, some viruses have alternative approaches involving posttranscriptional regulatory elements (PREs) to enhance intronless heterologous gene expression through enabling stability and 3′ end...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics