关键词: AngII BMI Beta-Galactosidase CHF COD CVD ECM EMT EPDC EndMT Epicardium-derived cells Fibrosis HHD Heart disease I/R IF LV MI MSC PFA RV SM TAC Tbx18 Tcf21 Wilms' tumor 1 Wt1 alpha Smooth Muscle Actin angiotensin II body mass index cardiovascular disease cause of death congestive heart failure endothelial–mesenchymal transition epicardium-derived cell epithelial–mesenchymal transition extracellular matrix hypertensive heart disease immunofluorescence ischemia/reperfusion left ventricle mesenchymal stem cell myocardial infarction paraformaldehyde right ventricle smooth muscle transverse aortic constriction αSMA βGal

Mesh : Adult Aged Aged, 80 and over Animals Basic Helix-Loop-Helix Transcription Factors / metabolism Biomarkers / metabolism Disease Models, Animal Endomyocardial Fibrosis / embryology metabolism pathology Heart Failure / complications metabolism pathology Humans Hypertension / complications embryology metabolism pathology Inflammation / metabolism pathology Leukocyte Common Antigens / metabolism Leukocytes / metabolism Mice Models, Biological Myocardial Ischemia / complications metabolism pathology Pericardium / embryology metabolism pathology Stem Cells / metabolism T-Box Domain Proteins / metabolism WT1 Proteins / metabolism

来  源:   DOI:10.1016/j.yjmcc.2013.10.005   PDF(Sci-hub)

Abstract:
During embryonic heart development, the transcription factors Tcf21, Wt1, and Tbx18 regulate activation and differentiation of epicardium-derived cells, including fibroblast lineages. Expression of these epicardial progenitor factors and localization of cardiac fibrosis were examined in mouse models of cardiovascular disease and in human diseased hearts. Following ischemic injury in mice, epicardial fibrosis is apparent in the thickened layer of subepicardial cells that express Wt1, Tbx18, and Tcf21. Perivascular fibrosis with predominant expression of Tcf21, but not Wt1 or Tbx18, occurs in mouse models of pressure overload or hypertensive heart disease, but not following ischemic injury. Areas of interstitial fibrosis in ischemic and hypertensive hearts actively express Tcf21, Wt1, and Tbx18. In all areas of fibrosis, cells that express epicardial progenitor factors are distinct from CD45-positive immune cells. In human diseased hearts, differential expression of Tcf21, Wt1, and Tbx18 also is detected with epicardial, perivascular, and interstitial fibrosis, indicating conservation of reactivated developmental mechanisms in cardiac fibrosis in mice and humans. Together, these data provide evidence for distinct fibrogenic mechanisms that include Tcf21, separate from Wt1 and Tbx18, in different fibroblast populations in response to specific types of cardiac injury.
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