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Expression of IL-1β, IL-1 receptor type I and IL-1 receptor antagonist in human aortic smooth muscle cells: effects of all-trans-retinoic acid
Örebro universitet, Institutionen för klinisk medicin.
Örebro universitet, Institutionen för klinisk medicin.
Örebro universitet, Institutionen för klinisk medicin.
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2006 (Engelska)Ingår i: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 43, nr 4, s. 377-382Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The proinflammatory cytokine interleukin (IL)-1β and the IL-1 receptor antagonist are expressed by atherosclerotic plaques and may be linked to the development of atherosclerosis. Existing evidence shows that retinoids and their receptors are involved in inflammatory response and that they are found in atherosclerotic plaques. In all-trans-retinoic acid (atRA)-treated human aortic smooth muscle cells (AOSMC), significant increases in IL-1β levels were observed, compared with untreated cells. Examination of IL-1 receptor antagonist and IL-1 receptor type I levels did not show any difference between atRA-treated and -untreated AOSMC. The results show that atRA-treated AOSMC express both the precursor (33 kDa) and the active form (17 kDa) of the IL-1β protein. atRA-treated carotid lesions showed significantly elevated IL-1β mRNA levels (2.9 ± 2.33) compared with untreated lesions (2.0 ± 1.77; p < 0.05). These results support the role of atRA as a regulator of inflammation such as in atherosclerosis.

Ort, förlag, år, upplaga, sidor
2006. Vol. 43, nr 4, s. 377-382
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Biomedicin
Identifikatorer
URN: urn:nbn:se:oru:diva-2843DOI: 10.1159/000094258OAI: oai:DiVA.org:oru-2843DiVA, id: diva2:134886
Tillgänglig från: 2007-05-11 Skapad: 2007-05-11 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
Ingår i avhandling
1. Retinoid metabolism and signalling in vascular smooth muscle cells
Öppna denna publikation i ny flik eller fönster >>Retinoid metabolism and signalling in vascular smooth muscle cells
2007 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Smooth muscle cells (SMCs) play a major role in cardiovascular diseases. In advanced atherosclerosis, blood flow is impaired due to reduced luminal diameter. Percutaneous vascular interventions, including balloon angioplasty and stent-application are commonly used for the re-establishment of luminal size and improvement of tissue perfusion. However, the benefit of vascular interventions is hampered by re-stenosis. The molecular basis of re-stenosis is not fully elucidated and so far, no successful treatment is clinically available. Re-stenosis, which is proposed to be a response to mechanical injury, involves the activation of multiple processes including inflammation, SMC migration and proliferation, and is characterized by vessel remodelling and intimal hyperplasia.

Retinoids have been shown to regulate several processes activated at site of vascular injury including inflammation, SMC migration and proliferation, and have been demonstrated to inhibit SMC proliferation and reduce intimal hyperplasia. Thus, retinoids are potential candidates in the treatment of certain vascular disorders. Retinoid metabolism is complex and involves a repertoire of proteins including retinoic acid synthesizing and catabolizing enzymes. The purpose of this study was to investigate retinoid metabolism in vascular cells, more specifically to find key points in the regulation of retinoid metabolism in vascular SMCs and atherosclerotic lesions.

We demonstrate that different phenotypes of SMCs exhibit differences in retinoid metabolism, which suggests a link between retinoid metabolism and the SMC phenotype. Vascular SMCs and atherosclerotic lesions expressed cytochrome P450 isoform 26 (CYP26) enzymes, which are involved in retinoid catabolism. Our studies reveal the presence of a negative feedback loop, in which retinoids induce its inactivation by inducing CYP26 expression in vascular SMCs and atherosclerotic lesions. Moreover, inhibition of CYP26 potently blocked retinoid catabolism and resulted in retinoid-like effects in SMCs, indicating that CYP26 is an important endogenous modulator of retinoid metabolism in vascular cells. In atherosclerotic lesions and vascular SMCs, decreased retinoid catabolism and hence, increased retinoid availability, resulted in increased expression of retinoid-responsive genes.

Since retinoids reduce intimal hyperplasia in animal models, our studies suggest that CYP26 inhibitors may provide an alternative to exogenous retinoid administration. Thus, CYP26 inhibitors may offer a new therapeutic approach to vascular proliferative disorders.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro universitetsbibliotek, 2007. s. 55
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 11
Nyckelord
all-trans Retinol, all-trans Retinoic acid, retinoid metabolism, proliferation, Vascular smooth muscle cells, CYP26
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Biomedicin
Identifikatorer
urn:nbn:se:oru:diva-1306 (URN)978-91-7668-541-9 (ISBN)
Disputation
2007-06-01, Hörsal P2, Prismahuset, Fakultetsgatan 1, Örebro, 10:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2007-05-11 Skapad: 2007-05-10 Senast uppdaterad: 2017-10-18Bibliografiskt granskad

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