TGF-β1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice

Andrew D. Frutkin, Goro Otsuka, April Stempien-Otero, Casilde Sesti, Liang Du, Mia Jaffe, Helén L. Dichek, Caroline J. Pennington, Dylan R. Edwards, Madeline Nieves-Cintrón, Daniel Minter, Michael Preusch, Jie Hong Hu, Julien C. Marie, David A. Dichek

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1251-1257
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number9
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Fingerprint

Transforming Growth Factors
Apolipoproteins E
Dilatation
Growth
Atherosclerosis
Cytokines
Lipids
Collagen
Matrix Metalloproteinase 13
Tissue Inhibitor of Metalloproteinase-2
False Aneurysm
Abdominal Aorta
Thoracic Aorta
Transgenes
Aneurysm
Aorta
Arteries
Lymphocytes
T-Lymphocytes
Gene Expression

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 journalArticle

Frutkin, AD, Otsuka, G, Stempien-Otero, A, Sesti, C, Du, L, Jaffe, M, Dichek, HL, Pennington, CJ, Edwards, DR, Nieves-Cintrón, M, Minter, D, Preusch, M, Hu, JH, Marie, JC & Dichek, DA 2009, 'TGF-β1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 9, pp. 1251-1257. https://doi.org/10.1161/ATVBAHA.109.186593
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. / TGF-β1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2009 ; Vol. 29, No. 9. pp. 1251-1257.
@article{ee3fef9615844c7bb72452cdf060a452,
title = "TGF-β1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice",
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.",
keywords = "Aneurysm, Atherosclerosis, Growth substances, Inflammation, Plaque",
author = "Frutkin, {Andrew D.} and Goro Otsuka and April Stempien-Otero and Casilde Sesti and Liang Du and Mia Jaffe and Dichek, {Hel{\'e}n L.} and Pennington, {Caroline J.} and Edwards, {Dylan R.} and Madeline Nieves-Cintr{\'o}n and Daniel Minter and Michael Preusch and Hu, {Jie Hong} and Marie, {Julien C.} and Dichek, {David A.}",
year = "2009",
month = "9",
day = "1",
doi = "10.1161/ATVBAHA.109.186593",
language = "English (US)",
volume = "29",
pages = "1251--1257",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

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 -