Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling

Shelley K. Miyasato, Jorik Loeffler, Ralph Shohet, Jianhua Zhang, Merry L Lindsey, Claude Jourdan Le Saux

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The cardiac response to myocardial injury includes fibrotic and hypertrophic processes and a key mediator in this response is transforming growth factor-β1 (TGF-β1). Caveolin-1 (cav1), the main structural protein of caveolae, is an inhibitor of the TGF-β1 signaling pathway. To examine the role of cav1 in cardiac repair, cav1 deficient (Cav1 -/-) and wild type (WT) mice were subjected to cryoinjury of the left ventricle (LV). At baseline the two groups exhibited no inflammation, similar collagen content, and similar cardiac function. After injury, Cav1 -/- animals displayed enhanced TGF-β1 signaling, as reflected by a 3-fold increase in the activation of the Smad2-dependent pathway and more widespread collagen deposition in the heart. Qualitative and quantitative analyses indicated that collagen deposition peaked in the WT LV 14days after injury, accompanied by increased mRNA abundance for procol1a2 (2-fold) and procol3a1 (3-fold). Collagen deposition was further enhanced in Cav1 -/- mice, which was accompanied by reduced expression of matrix metalloproteinases MMP-8 (3-fold) and -13 mRNA (2-fold). The levels of expression of inflammatory markers of acute phase were similar between the strains However, macrophage clearance in the damaged region was delayed in Cav1 -/- mice. We observed a 4-fold decrease in collagen deposition in Cav1 -/- mice injected with a cav1 scaffolding domain peptide (CSD) and a 2-fold decrease in WT mice treated with the CSD. We conclude that cav1 has a direct role in reducing TGF-β1 signaling and as such might be an appropriate target for therapies to influence cardiac remodeling.

Original languageEnglish (US)
Pages (from-to)318-329
Number of pages12
JournalMatrix Biology
Volume30
Issue number5-6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Caveolin 1
Transforming Growth Factors
Collagen
Heart Ventricles
Wounds and Injuries
Matrix Metalloproteinase 8
Caveolae
Messenger RNA
Matrix Metalloproteinases
Macrophages
Inflammation
Proteins

Keywords

  • Cardiac remodeling
  • Caveolin-1
  • Cryoinjury
  • Mouse model
  • TGF-β1 signaling

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Miyasato, S. K., Loeffler, J., Shohet, R., Zhang, J., Lindsey, M. L., & Le Saux, C. J. (2011). Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. Matrix Biology, 30(5-6), 318-329. https://doi.org/10.1016/j.matbio.2011.05.003

Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. / Miyasato, Shelley K.; Loeffler, Jorik; Shohet, Ralph; Zhang, Jianhua; Lindsey, Merry L; Le Saux, Claude Jourdan.

In: Matrix Biology, Vol. 30, No. 5-6, 01.06.2011, p. 318-329.

Research output: Contribution to journalArticle

Miyasato, SK, Loeffler, J, Shohet, R, Zhang, J, Lindsey, ML & Le Saux, CJ 2011, 'Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling', Matrix Biology, vol. 30, no. 5-6, pp. 318-329. https://doi.org/10.1016/j.matbio.2011.05.003
Miyasato SK, Loeffler J, Shohet R, Zhang J, Lindsey ML, Le Saux CJ. Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. Matrix Biology. 2011 Jun 1;30(5-6):318-329. https://doi.org/10.1016/j.matbio.2011.05.003
Miyasato, Shelley K. ; Loeffler, Jorik ; Shohet, Ralph ; Zhang, Jianhua ; Lindsey, Merry L ; Le Saux, Claude Jourdan. / Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. In: Matrix Biology. 2011 ; Vol. 30, No. 5-6. pp. 318-329.
@article{93e4d121698a4e28970f0108039b325d,
title = "Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling",
abstract = "The cardiac response to myocardial injury includes fibrotic and hypertrophic processes and a key mediator in this response is transforming growth factor-β1 (TGF-β1). Caveolin-1 (cav1), the main structural protein of caveolae, is an inhibitor of the TGF-β1 signaling pathway. To examine the role of cav1 in cardiac repair, cav1 deficient (Cav1 -/-) and wild type (WT) mice were subjected to cryoinjury of the left ventricle (LV). At baseline the two groups exhibited no inflammation, similar collagen content, and similar cardiac function. After injury, Cav1 -/- animals displayed enhanced TGF-β1 signaling, as reflected by a 3-fold increase in the activation of the Smad2-dependent pathway and more widespread collagen deposition in the heart. Qualitative and quantitative analyses indicated that collagen deposition peaked in the WT LV 14days after injury, accompanied by increased mRNA abundance for procol1a2 (2-fold) and procol3a1 (3-fold). Collagen deposition was further enhanced in Cav1 -/- mice, which was accompanied by reduced expression of matrix metalloproteinases MMP-8 (3-fold) and -13 mRNA (2-fold). The levels of expression of inflammatory markers of acute phase were similar between the strains However, macrophage clearance in the damaged region was delayed in Cav1 -/- mice. We observed a 4-fold decrease in collagen deposition in Cav1 -/- mice injected with a cav1 scaffolding domain peptide (CSD) and a 2-fold decrease in WT mice treated with the CSD. We conclude that cav1 has a direct role in reducing TGF-β1 signaling and as such might be an appropriate target for therapies to influence cardiac remodeling.",
keywords = "Cardiac remodeling, Caveolin-1, Cryoinjury, Mouse model, TGF-β1 signaling",
author = "Miyasato, {Shelley K.} and Jorik Loeffler and Ralph Shohet and Jianhua Zhang and Lindsey, {Merry L} and {Le Saux}, {Claude Jourdan}",
year = "2011",
month = "6",
day = "1",
doi = "10.1016/j.matbio.2011.05.003",
language = "English (US)",
volume = "30",
pages = "318--329",
journal = "Matrix Biology",
issn = "0945-053X",
publisher = "Elsevier",
number = "5-6",

}

TY - JOUR

T1 - Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling

AU - Miyasato, Shelley K.

AU - Loeffler, Jorik

AU - Shohet, Ralph

AU - Zhang, Jianhua

AU - Lindsey, Merry L

AU - Le Saux, Claude Jourdan

PY - 2011/6/1

Y1 - 2011/6/1

N2 - The cardiac response to myocardial injury includes fibrotic and hypertrophic processes and a key mediator in this response is transforming growth factor-β1 (TGF-β1). Caveolin-1 (cav1), the main structural protein of caveolae, is an inhibitor of the TGF-β1 signaling pathway. To examine the role of cav1 in cardiac repair, cav1 deficient (Cav1 -/-) and wild type (WT) mice were subjected to cryoinjury of the left ventricle (LV). At baseline the two groups exhibited no inflammation, similar collagen content, and similar cardiac function. After injury, Cav1 -/- animals displayed enhanced TGF-β1 signaling, as reflected by a 3-fold increase in the activation of the Smad2-dependent pathway and more widespread collagen deposition in the heart. Qualitative and quantitative analyses indicated that collagen deposition peaked in the WT LV 14days after injury, accompanied by increased mRNA abundance for procol1a2 (2-fold) and procol3a1 (3-fold). Collagen deposition was further enhanced in Cav1 -/- mice, which was accompanied by reduced expression of matrix metalloproteinases MMP-8 (3-fold) and -13 mRNA (2-fold). The levels of expression of inflammatory markers of acute phase were similar between the strains However, macrophage clearance in the damaged region was delayed in Cav1 -/- mice. We observed a 4-fold decrease in collagen deposition in Cav1 -/- mice injected with a cav1 scaffolding domain peptide (CSD) and a 2-fold decrease in WT mice treated with the CSD. We conclude that cav1 has a direct role in reducing TGF-β1 signaling and as such might be an appropriate target for therapies to influence cardiac remodeling.

AB - The cardiac response to myocardial injury includes fibrotic and hypertrophic processes and a key mediator in this response is transforming growth factor-β1 (TGF-β1). Caveolin-1 (cav1), the main structural protein of caveolae, is an inhibitor of the TGF-β1 signaling pathway. To examine the role of cav1 in cardiac repair, cav1 deficient (Cav1 -/-) and wild type (WT) mice were subjected to cryoinjury of the left ventricle (LV). At baseline the two groups exhibited no inflammation, similar collagen content, and similar cardiac function. After injury, Cav1 -/- animals displayed enhanced TGF-β1 signaling, as reflected by a 3-fold increase in the activation of the Smad2-dependent pathway and more widespread collagen deposition in the heart. Qualitative and quantitative analyses indicated that collagen deposition peaked in the WT LV 14days after injury, accompanied by increased mRNA abundance for procol1a2 (2-fold) and procol3a1 (3-fold). Collagen deposition was further enhanced in Cav1 -/- mice, which was accompanied by reduced expression of matrix metalloproteinases MMP-8 (3-fold) and -13 mRNA (2-fold). The levels of expression of inflammatory markers of acute phase were similar between the strains However, macrophage clearance in the damaged region was delayed in Cav1 -/- mice. We observed a 4-fold decrease in collagen deposition in Cav1 -/- mice injected with a cav1 scaffolding domain peptide (CSD) and a 2-fold decrease in WT mice treated with the CSD. We conclude that cav1 has a direct role in reducing TGF-β1 signaling and as such might be an appropriate target for therapies to influence cardiac remodeling.

KW - Cardiac remodeling

KW - Caveolin-1

KW - Cryoinjury

KW - Mouse model

KW - TGF-β1 signaling

UR - http://www.scopus.com/inward/record.url?scp=79960561895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960561895&partnerID=8YFLogxK

U2 - 10.1016/j.matbio.2011.05.003

DO - 10.1016/j.matbio.2011.05.003

M3 - Article

VL - 30

SP - 318

EP - 329

JO - Matrix Biology

JF - Matrix Biology

SN - 0945-053X

IS - 5-6

ER -