OBJECTIVE: Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. METHODS: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage, SMC content and intraplaque thrombus amount were determined histologically. FoxP1 expression was investigated by western blotting and immunohistochemistry. In addition FoxP1 was overexpressed in vitro to identify causal relations between FoxP1 and plaque proteins. RESULTS: FoxP1 expression was observed in SMCs, macrophages, endothelial cells and T-cells within the plaque. High SMC and collagen content correlated with increased FoxP1 isoform (72 kD and 95 kD) levels. 72 kD FoxP1 expression was lower in plaques containing intraplaque thrombus. FoxP1 correlated with active intraplaque TGFβ signaling. In vitro stimulation of SMCs with TGFβ resulted in increased FoxP1 levels. 72 kD FoxP1 correlated with expression of pro-fibrotic EGR-1 and increased Col1A1 expression. CONCLUSION: FoxP1 is expressed by different cell types in atherosclerotic lesions and associated with more stable plaque characteristics and intraplaque TGFβ signaling. FoxP1 expression in vitro is induced by TGFβ, resulting in increased collagen and EGR-1 expression, providing a mechanism for the observed association with a more stable plaque phenotype.
OBJECTIVE:Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. METHODS: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage, SMC content and intraplaque thrombus amount were determined histologically. FoxP1 expression was investigated by western blotting and immunohistochemistry. In addition FoxP1 was overexpressed in vitro to identify causal relations between FoxP1 and plaque proteins. RESULTS:FoxP1 expression was observed in SMCs, macrophages, endothelial cells and T-cells within the plaque. High SMC and collagen content correlated with increased FoxP1 isoform (72 kD and 95 kD) levels. 72 kD FoxP1 expression was lower in plaques containing intraplaque thrombus. FoxP1 correlated with active intraplaque TGFβ signaling. In vitro stimulation of SMCs with TGFβ resulted in increased FoxP1 levels. 72 kD FoxP1 correlated with expression of pro-fibrotic EGR-1 and increased Col1A1 expression. CONCLUSION:FoxP1 is expressed by different cell types in atherosclerotic lesions and associated with more stable plaque characteristics and intraplaque TGFβ signaling. FoxP1 expression in vitro is induced by TGFβ, resulting in increased collagen and EGR-1 expression, providing a mechanism for the observed association with a more stable plaque phenotype.
Authors: Boxiang Liu; Milos Pjanic; Ting Wang; Trieu Nguyen; Michael Gloudemans; Abhiram Rao; Victor G Castano; Sylvia Nurnberg; Daniel J Rader; Susannah Elwyn; Erik Ingelsson; Stephen B Montgomery; Clint L Miller; Thomas Quertermous Journal: Am J Hum Genet Date: 2018-08-23 Impact factor: 11.025
Authors: Wolfgang Lieb; Ming-Huei Chen; Alexander Teumer; Rudolf A de Boer; Honghuang Lin; Ervin R Fox; Solomon K Musani; James G Wilson; Thomas J Wang; Henry Völzke; Ann-Kristin Petersen; Christine Meisinger; Matthias Nauck; Sabrina Schlesinger; Yong Li; Jöel Menard; Serge Hercberg; H-Erich Wichmann; Uwe Völker; Rajesh Rawal; Martin Bidlingmaier; Anke Hannemann; Marcus Dörr; Rainer Rettig; Wiek H van Gilst; Dirk J van Veldhuisen; Stephan J L Bakker; Gerjan Navis; Henri Wallaschofski; Pierre Meneton; Pim van der Harst; Martin Reincke; Ramachandran S Vasan Journal: Circ Cardiovasc Genet Date: 2014-12-04
Authors: Kurt Reifenberg; Fei Cheng; Carolin Orning; Jeanine Crain; Ines Küpper; Elena Wiese; Martina Protschka; Manfred Blessing; Karl J Lackner; Michael Torzewski Journal: PLoS One Date: 2012-07-19 Impact factor: 3.240