Abstract
OBJECTIVE-: Impairment of transforming growth factor (TGF)-β1 signaling accelerates atherosclerosis in experimental mice. However, it is uncertain whether increased TGF-β1 expression would retard atherosclerosis. The role of TGF-β1 in aneurysm formation is also controversial. We tested whether overexpression of active TGF-β1 in hyperlipidemic mice affects atherogenesis and aortic dilation. METHODS AND RESULTS-: We generated apolipoprotein E-null mice with transgenes that allow regulated overexpression of active TGF-β1 in their hearts. Compared to littermate controls, these mice had elevated cardiac and plasma TGF-β1, less aortic root atherosclerosis (P≤0.002), fewer lesions in the thoracic and abdominal aortae (P≤0.01), less aortic root dilation (P<0.001), and fewer pseudoaneurysms (P=0.02). Mechanistic studies revealed no effect of TGF-β1 overexpression on plasma lipids or cytokines, or on peripheral lymphoid organ cells. However, aortae of TGF-β1-overexpressing mice had fewer T-lymphocytes, more collagen, less lipid, lower expression of inflammatory cytokines and matrix metalloproteinase-13, and higher expression of tissue inhibitor of metalloproteinase-2. CONCLUSIONS-: When overexpressed in the heart and plasma, TGF-β1 is an antiatherogenic, vasculoprotective cytokine that limits atherosclerosis and prevents aortic dilation. These actions are associated with significant changes in cellularity, collagen and lipid accumulation, and gene expression in the artery wall.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1251-1257 |
| Number of pages | 7 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 29 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2009 |
| Externally published | Yes |
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Keywords
- Aneurysm
- Atherosclerosis
- Growth substances
- Inflammation
- Plaque
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
TGF-β1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice. / Frutkin, Andrew D.; Otsuka, Goro; Stempien-Otero, April; Sesti, Casilde; Du, Liang; Jaffe, Mia; Dichek, Helén L.; Pennington, Caroline J.; Edwards, Dylan R.; Nieves-Cintrón, Madeline; Minter, Daniel; Preusch, Michael; Hu, Jie Hong; Marie, Julien C.; Dichek, David A.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 29, No. 9, 01.09.2009, p. 1251-1257.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TGF-β1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice
AU - Frutkin, Andrew D.
AU - Otsuka, Goro
AU - Stempien-Otero, April
AU - Sesti, Casilde
AU - Du, Liang
AU - Jaffe, Mia
AU - Dichek, Helén L.
AU - Pennington, Caroline J.
AU - Edwards, Dylan R.
AU - Nieves-Cintrón, Madeline
AU - Minter, Daniel
AU - Preusch, Michael
AU - Hu, Jie Hong
AU - Marie, Julien C.
AU - Dichek, David A.
PY - 2009/9/1
Y1 - 2009/9/1
N2 - OBJECTIVE-: Impairment of transforming growth factor (TGF)-β1 signaling accelerates atherosclerosis in experimental mice. However, it is uncertain whether increased TGF-β1 expression would retard atherosclerosis. The role of TGF-β1 in aneurysm formation is also controversial. We tested whether overexpression of active TGF-β1 in hyperlipidemic mice affects atherogenesis and aortic dilation. METHODS AND RESULTS-: We generated apolipoprotein E-null mice with transgenes that allow regulated overexpression of active TGF-β1 in their hearts. Compared to littermate controls, these mice had elevated cardiac and plasma TGF-β1, less aortic root atherosclerosis (P≤0.002), fewer lesions in the thoracic and abdominal aortae (P≤0.01), less aortic root dilation (P<0.001), and fewer pseudoaneurysms (P=0.02). Mechanistic studies revealed no effect of TGF-β1 overexpression on plasma lipids or cytokines, or on peripheral lymphoid organ cells. However, aortae of TGF-β1-overexpressing mice had fewer T-lymphocytes, more collagen, less lipid, lower expression of inflammatory cytokines and matrix metalloproteinase-13, and higher expression of tissue inhibitor of metalloproteinase-2. CONCLUSIONS-: When overexpressed in the heart and plasma, TGF-β1 is an antiatherogenic, vasculoprotective cytokine that limits atherosclerosis and prevents aortic dilation. These actions are associated with significant changes in cellularity, collagen and lipid accumulation, and gene expression in the artery wall.
AB - OBJECTIVE-: Impairment of transforming growth factor (TGF)-β1 signaling accelerates atherosclerosis in experimental mice. However, it is uncertain whether increased TGF-β1 expression would retard atherosclerosis. The role of TGF-β1 in aneurysm formation is also controversial. We tested whether overexpression of active TGF-β1 in hyperlipidemic mice affects atherogenesis and aortic dilation. METHODS AND RESULTS-: We generated apolipoprotein E-null mice with transgenes that allow regulated overexpression of active TGF-β1 in their hearts. Compared to littermate controls, these mice had elevated cardiac and plasma TGF-β1, less aortic root atherosclerosis (P≤0.002), fewer lesions in the thoracic and abdominal aortae (P≤0.01), less aortic root dilation (P<0.001), and fewer pseudoaneurysms (P=0.02). Mechanistic studies revealed no effect of TGF-β1 overexpression on plasma lipids or cytokines, or on peripheral lymphoid organ cells. However, aortae of TGF-β1-overexpressing mice had fewer T-lymphocytes, more collagen, less lipid, lower expression of inflammatory cytokines and matrix metalloproteinase-13, and higher expression of tissue inhibitor of metalloproteinase-2. CONCLUSIONS-: When overexpressed in the heart and plasma, TGF-β1 is an antiatherogenic, vasculoprotective cytokine that limits atherosclerosis and prevents aortic dilation. These actions are associated with significant changes in cellularity, collagen and lipid accumulation, and gene expression in the artery wall.
KW - Aneurysm
KW - Atherosclerosis
KW - Growth substances
KW - Inflammation
KW - Plaque
UR - http://www.scopus.com/inward/record.url?scp=69849094786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69849094786&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.109.186593
DO - 10.1161/ATVBAHA.109.186593
M3 - Article
C2 - 19325140
AN - SCOPUS:69849094786
VL - 29
SP - 1251
EP - 1257
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 9
ER -