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  • 1
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    Role of prostacyclin in the cardiovascular response to thromboxane A2 (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-04-20
    Description: Thromboxane (Tx) A2 is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI2) is a vasodilator that inhibits platelet function. Here we show that injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the PGI2 receptor (IP) but are depressed in mice genetically deficient in the TxA2 receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI2 modulates platelet-vascular interactions in vivo and specifically limits the response to TxA2. This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), inhibit PGI2 but not TxA2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Yan -- Austin, Sandra C -- Rocca, Bianca -- Koller, Beverly H -- Coffman, Thomas M -- Grosser, Tilo -- Lawson, John A -- FitzGerald, Garret A -- HL 54500/HL/NHLBI NIH HHS/ -- HL 62250/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Apr 19;296(5567):539-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Experimental Therapeutics, 153 Johnson Pavilion, 3620 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11964481" target="_blank"〉PubMed〈/a〉
    Keywords: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Animals ; *Carotid Artery Injuries/pathology ; Carotid Artery, Common/cytology/drug effects/physiology ; Cell Division ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/adverse effects/therapeutic use ; Endothelium, Vascular/cytology/drug effects/*physiology ; Epoprostenol/metabolism/*physiology ; Humans ; Isoenzymes/antagonists & inhibitors ; Lactones/adverse effects/therapeutic use ; Male ; Membrane Proteins ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Muscle, Smooth, Vascular/cytology/drug effects/physiology ; Naphthalenes ; *Platelet Activation/drug effects ; Platelet Aggregation/drug effects ; Propionates ; Prostaglandin-Endoperoxide Synthases ; Receptors, Epoprostenol ; Receptors, Prostaglandin/physiology ; Receptors, Thromboxane/antagonists & inhibitors/genetics/physiology ; Sulfones ; Tetrahydronaphthalenes/pharmacology ; Thromboxane A2/*physiology ; Tunica Intima/cytology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    COX-2-derived prostacyclin confers atheroprotection on female mice (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-11-20
    Description: Female gender affords relative protection from cardiovascular disease until the menopause. We report that estrogen acts on estrogen receptor subtype alpha to up-regulate the production of atheroprotective prostacyclin, PGI2, by activation of cyclooxygenase 2 (COX-2). This mechanism restrained both oxidant stress and platelet activation that contribute to atherogenesis in female mice. Deletion of the PGI2 receptor removed the atheroprotective effect of estrogen in ovariectomized female mice. This suggests that chronic treatment of patients with selective inhibitors of COX-2 could undermine protection from cardiovascular disease in premenopausal females.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Egan, Karine M -- Lawson, John A -- Fries, Susanne -- Koller, Beverley -- Rader, Daniel J -- Smyth, Emer M -- Fitzgerald, Garret A -- HL62250/HL/NHLBI NIH HHS/ -- HL70128/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1954-7. Epub 2004 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15550624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antioxidants/metabolism ; Arteriosclerosis/metabolism/pathology/*prevention & control ; Cardiovascular Diseases/chemically induced ; Cells, Cultured ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/adverse effects/pharmacology ; Epoprostenol/biosynthesis/metabolism/*physiology ; Estradiol/pharmacology ; Estrogen Receptor alpha/metabolism ; Female ; Hydrogen Peroxide/pharmacology ; Isoenzymes/*metabolism ; Lactones/adverse effects/pharmacology ; Lipid Peroxidation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular/drug effects/metabolism ; Myocytes, Smooth Muscle/cytology/drug effects/metabolism ; Ovariectomy ; Oxidative Stress ; Platelet Activation ; Prostaglandin-Endoperoxide Synthases/*metabolism ; Receptors, Epoprostenol/genetics/physiology ; Receptors, LDL/genetics/physiology ; Sex Characteristics ; Sulfones/adverse effects/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
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