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Endothelin receptor...
Endothelin receptor antagonist macitentan or deletion of mouse mast cell protease 4 delays lesion development in atherosclerotic mice
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- Houde, Martin (författare)
- Univ Sherbrooke, Dept Pharmacol, 3001 12e Ave Nord, Sherbrooke, PQ, Canada.
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- Desbiens, Louisane (författare)
- Univ Sherbrooke, Dept Pharmacol, 3001 12e Ave Nord, Sherbrooke, PQ, Canada.
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- Schwertani, Adel (författare)
- McGill Univ, Dept Cardiol, Montreal, PQ, Canada.
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- Pejler, Gunnar (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
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- Iglarz, Marc (författare)
- Actel Pharmaceut Ltd, Drug Discovery Dept, Allschwil, Switzerland.
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- D'Orleans-Juste, Pedro (författare)
- Univ Sherbrooke, Dept Pharmacol, 3001 12e Ave Nord, Sherbrooke, PQ, Canada.
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Univ Sherbrooke, Dept Pharmacol, 3001 12e Ave Nord, Sherbrooke, PQ, Canada McGill Univ, Dept Cardiol, Montreal, PQ, Canada. (creator_code:org_t)
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- PERGAMON-ELSEVIER SCIENCE LTD, 2016
- 2016
- Engelska.
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Ingår i: Life Sciences. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0024-3205 .- 1879-0631. ; 159, s. 71-75
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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Abstract
Ämnesord
Stäng
- Aims: To determine the impact of mixed endothelin receptor antagonist and mouse mast cell protease-4 (mMCP-4) in the development of atherosclerosis in the mouse model. Materials and methods: Apolipoprotein E (ApoE) KO mice were crossed with mMCP-4 KO mice to generate ApoE/mMCP-4 double KO mice. Atherosclerosis was induced with a normal- or high-fat diet for 12, 27 or 52 weeks. Macitentan (30 mg/kg/day), a dual ETA/ETB receptor antagonist, was given orally for 6 weeks (27 week protocol). At sacrifice, aortas and brachiocephalic arteries (BCAs) were collected. En lace Sudan IV staining was performed on aortas and BCA sections were subjected to Masson's trichrome stain and a.-smooth muscle actin labeling. Key findings: Under normal diet, both macitentan treatment and the absence of mMCP-4 reduced the development of aortic atherosclerotic lesions in 27-week old ApoE KO mice, but mMCP-4 deletion failed to maintain this effect on 52-week old mice. Under high-fat diet (WD), macitentan, but not the absence of mMCP-4, reduced aortic lesion development in ApoE KO mice. On BCA lesions of 27-week old WD mice, macitentan treatment had a small impact while mMCP-4 deletion showed improved features of plaque stability. Significance: These results suggest that the inhibition of mMCP-4 reduces lesion spreading in the earlier phases of atherosclerosis development and can help stabilise the more advanced plaque. Macitentan treatment was more effective to prevent lesion spreading but did not improve plaque features to the same extent.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Atherosclerosis
- Endothelin
- Chymase
- Apolipoprotein E
- Macitentan
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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