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Uremia modulates th...
Uremia modulates the phenotype of aortic smooth muscle cells
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- Madsen, Marie (author)
- University of Copenhagen
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- Aarup, Annemarie (author)
- University of Copenhagen
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- Albinsson, Sebastian (author)
- Lund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups
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- Hartvigsen, Karsten (author)
- University of Copenhagen
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- Sørensen, Charlotte M. (author)
- University of Copenhagen
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- Turczynska, Karolina (author)
- Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups
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- Nielsen, Lars B. (author)
- Copenhagen University Hospital,University of Copenhagen
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- Pedersen, Tanja Xenia (author)
- University of Copenhagen
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 257, s. 64-70
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http://dx.doi.org/10...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Background and aims Chronic kidney disease leads to uremia and markedly accelerates atherosclerosis. Phenotypic modulation of smooth muscle cells (SMCs) in the arterial media plays a key role in accelerating atherogenesis. The aim of this study was to investigate whether uremia per se modulates the phenotype of aortic SMCs in vivo. Methods Moderate uremia was induced by 5/6 nephrectomy in apolipoprotein E knockout (ApoE-/-) and wildtype C57Bl/6 mice. Plasma analysis, gene expression, histology, and myography were used to determine uremia-mediated changes in the arterial wall. Results Induction of moderate uremia in ApoE-/- mice increased atherosclerosis in the aortic arch en face 1.6 fold (p = 0.04) and induced systemic inflammation. Based on histological analyses of aortic root sections, uremia increased the medial area, while there was no difference in the content of elastic fibers or collagen in the aortic media. In the aortic arch, mRNA and miRNA expression patterns were consistent with a uremia-mediated phenotypic modulation of SMCs; e.g. downregulation of myocardin, α-smooth muscle actin, and transgelin; and upregulation of miR146a. Notably, these expression patterns were observed after acute (2 weeks) and chronic (19 and 30 weeks) uremia, both under normo- and hypercholesterolemic settings. Functionally, aortic constriction was decreased in uremic as compared to non-uremic aorta segments, as measured by myography. Conclusions Uremia modulates the phenotype of aortic SMCs as determined by mRNA/miRNA expression, an increased medial area, and decreased aortic contractility. We propose that this phenotypic modulation of SMCs precedes the acceleration of atherosclerosis observed in uremic mice.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Phenotypic modulation
- Smooth muscle cells
- Uremia
Publication and Content Type
- art (subject category)
- ref (subject category)
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