| Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis. | |
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MedLine Citation:
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PMID: 21148758 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Thromboxane A2 and other eicosanoids such as isoprostanes, binding to the thromboxane/prostaglandin endoperoxide receptors (TPr), contribute to vascular proliferation and atherosclerosis. The effects of terutroban, a TPr antagonist, were evaluated on aorta remodelling, in spontaneously hypertensive stroke-prone rats (SHRSPs), a model of severe hypertension, endothelial dysfunction, vascular inflammation and cerebrovascular diseases. Male SHRSPs were allocated to three groups receiving standard diet (n=5), high-sodium permissive-diet plus vehicle (n=6) or plus terutroban (30 mg/kg/day; n=6). After six weeks of dietary treatment, all the animals were injected with bromodeoxyuridine (BrdU) and simultaneously euthanized for aorta collection. The aortic media thickness/lumen ratio significantly (p<0.0001) increased in salt-loaded rats compared with the standard diet-fed rats, while terutroban treatment completely prevented media thickening (p<0.001). Compared with vehicle, terutroban was also effective in preventing cell proliferation in the media, as indicated by a reduced number of BrdU positive (p<0.0001) and proliferating-cell-nuclear-antigen positive cells (p<0.0001). A severe fibrosis, characterized by a significant accumulation of collagen and fibronectin in the vascular wall, was recorded in vehicle-treated rats (p<0.01) but was completely prevented by terutroban (p<0.001). The latter also inhibits heat-shock protein (HSP)47 (p<0.01) and transforming growth factor (TGF)-1β expression (p<0.001) that were significantly increased by high-salt diet. In conclusion, terutroban prevents the development of aorta hyperplasia besides exerting a benefit on fibrotic processes via an effect on TGF-beta and HSP-47 expression in SHRSP. These findings provide mechanistic data to support the beneficial effects exerted by terutroban in preventing or retarding atherogenesis. |
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Authors:
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Paolo Gelosa; Gulnur Sevin; Alice Pignieri; Silvia Budelli; Laura Castiglioni; Vanessa Blanc-Guillemaud; Laurence Lerond; Elena Tremoli; Luigi Sironi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-12-10 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Milan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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