Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.
Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/1aafe7beccd9466fb404097518dcf340 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:1aafe7beccd9466fb404097518dcf340 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:1aafe7beccd9466fb404097518dcf3402021-11-18T07:11:51ZOverexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.1932-620310.1371/journal.pone.0040990https://doaj.org/article/1aafe7beccd9466fb404097518dcf3402012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22829904/?tool=EBIhttps://doaj.org/toc/1932-6203Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E) knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE(-/-) mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet) as indicated by aortic plaque area en face (p<0.05). Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD), significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD), significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively) without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.Kurt ReifenbergFei ChengCarolin OrningJeanine CrainInes KüpperElena WieseMartina ProtschkaManfred BlessingKarl J LacknerMichael TorzewskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e40990 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Kurt Reifenberg Fei Cheng Carolin Orning Jeanine Crain Ines Küpper Elena Wiese Martina Protschka Manfred Blessing Karl J Lackner Michael Torzewski Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. |
| description |
Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E) knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE(-/-) mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet) as indicated by aortic plaque area en face (p<0.05). Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD), significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD), significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively) without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. |
| format |
article |
| author |
Kurt Reifenberg Fei Cheng Carolin Orning Jeanine Crain Ines Küpper Elena Wiese Martina Protschka Manfred Blessing Karl J Lackner Michael Torzewski |
| author_facet |
Kurt Reifenberg Fei Cheng Carolin Orning Jeanine Crain Ines Küpper Elena Wiese Martina Protschka Manfred Blessing Karl J Lackner Michael Torzewski |
| author_sort |
Kurt Reifenberg |
| title |
Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. |
| title_short |
Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. |
| title_full |
Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. |
| title_fullStr |
Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. |
| title_full_unstemmed |
Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. |
| title_sort |
overexpression of tgf-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in apoe-deficient mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/1aafe7beccd9466fb404097518dcf340 |
| work_keys_str_mv |
AT kurtreifenberg overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT feicheng overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT carolinorning overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT jeaninecrain overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT ineskupper overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT elenawiese overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT martinaprotschka overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT manfredblessing overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT karljlackner overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice AT michaeltorzewski overexpressionoftgfß1inmacrophagesreducesandstabilizesatheroscleroticplaquesinapoedeficientmice |
| _version_ |
1718423773610246144 |