| First Author | Reifenberg K | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 7 | Pages | e40990 |
| PubMed ID | 22829904 | Mgi Jnum | J:189586 |
| Mgi Id | MGI:5446532 | Doi | 10.1371/journal.pone.0040990 |
| Citation | Reifenberg K, et al. (2012) Overexpression of TGF-ss1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. PLoS One 7(7):e40990 |
| abstractText | Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ss1 (transforming growth factor beta1) 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. |
