The role of transforming growth factor (TGF)-β in the infarcted myocardium

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

The adult mammalian heart has negligible regenerative capacity. Following myocardial infarction, sudden necrosis of cardiomyocytes triggers an intense inflammatory reaction that clears the wound from dead cells and matrix debris, while activating a reparative program. A growing body of evidence suggests that members of the transforming growth factor (TGF)-β family critically regulate the inflammatory and reparative response following infarction. Although all three TGF-β isoforms (TGF-β1, -β2 and -β3) are markedly upregulated in the infarcted myocardium, information on isoform-specific actions is limited. Experimental studies have suggested that TGF-β exerts a wide range of actions on cardiomyocytes, fibroblasts, immune cells, and vascular cells. The findings are often conflicting, reflecting the contextdependence of TGF-β-mediated effects; conclusions are often based exclusively on in vitro studies and on associative evidence. TGF-β has been reported to modulate cardiomyocyte survival responses, promote monocyte recruitment, inhibit macrophage pro-inflammatory gene expression, suppress adhesion molecule synthesis by endothelial cells, promote myofibroblast conversion and extracellular matrix synthesis, and mediate both angiogenic and angiostatic effects. This review manuscript discusses our understanding of the cell biological effects of TGF-β in myocardial infarction. We discuss the relative significance of downstream TGF-β-mediated Smad-dependent and -independent pathways, and the risks and challenges of therapeutic TGF-β targeting. Considering the high significance of TGF-β-mediated actions in vivo, study of cell-specific effects and dissection of downstream signaling pathways are needed in order to design safe and effective therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)S52-S63
JournalJournal of Thoracic Disease
Volume9
DOIs
StatePublished - Mar 1 2017

Fingerprint

Transforming Growth Factors
Myocardium
Cardiac Myocytes
Protein Isoforms
Myocardial Infarction
Myofibroblasts
Manuscripts
Infarction
Extracellular Matrix
Blood Vessels
Dissection
Monocytes
Necrosis
Endothelial Cells
Fibroblasts
Macrophages
Gene Expression
Wounds and Injuries

Keywords

  • Cardiac remodeling
  • Cardiomyocyte
  • Fibroblast
  • Inflammation
  • Myocardial infarction
  • Transforming growth factor-beta (TGF-β)

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

The role of transforming growth factor (TGF)-β in the infarcted myocardium. / Frangogiannis, Nikolaos G.

In: Journal of Thoracic Disease, Vol. 9, 01.03.2017, p. S52-S63.

Research output: Contribution to journalReview article

@article{cf0455f9fb114f658203a1aa524782f2,
title = "The role of transforming growth factor (TGF)-β in the infarcted myocardium",
abstract = "The adult mammalian heart has negligible regenerative capacity. Following myocardial infarction, sudden necrosis of cardiomyocytes triggers an intense inflammatory reaction that clears the wound from dead cells and matrix debris, while activating a reparative program. A growing body of evidence suggests that members of the transforming growth factor (TGF)-β family critically regulate the inflammatory and reparative response following infarction. Although all three TGF-β isoforms (TGF-β1, -β2 and -β3) are markedly upregulated in the infarcted myocardium, information on isoform-specific actions is limited. Experimental studies have suggested that TGF-β exerts a wide range of actions on cardiomyocytes, fibroblasts, immune cells, and vascular cells. The findings are often conflicting, reflecting the contextdependence of TGF-β-mediated effects; conclusions are often based exclusively on in vitro studies and on associative evidence. TGF-β has been reported to modulate cardiomyocyte survival responses, promote monocyte recruitment, inhibit macrophage pro-inflammatory gene expression, suppress adhesion molecule synthesis by endothelial cells, promote myofibroblast conversion and extracellular matrix synthesis, and mediate both angiogenic and angiostatic effects. This review manuscript discusses our understanding of the cell biological effects of TGF-β in myocardial infarction. We discuss the relative significance of downstream TGF-β-mediated Smad-dependent and -independent pathways, and the risks and challenges of therapeutic TGF-β targeting. Considering the high significance of TGF-β-mediated actions in vivo, study of cell-specific effects and dissection of downstream signaling pathways are needed in order to design safe and effective therapeutic approaches.",
keywords = "Cardiac remodeling, Cardiomyocyte, Fibroblast, Inflammation, Myocardial infarction, Transforming growth factor-beta (TGF-β)",
author = "Frangogiannis, {Nikolaos G.}",
year = "2017",
month = "3",
day = "1",
doi = "10.21037/jtd.2016.11.19",
language = "English (US)",
volume = "9",
pages = "S52--S63",
journal = "Journal of Thoracic Disease",
issn = "2072-1439",
publisher = "Pioneer Bioscience Publishing Company (PBPC)",

}

TY - JOUR

T1 - The role of transforming growth factor (TGF)-β in the infarcted myocardium

AU - Frangogiannis, Nikolaos G.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - The adult mammalian heart has negligible regenerative capacity. Following myocardial infarction, sudden necrosis of cardiomyocytes triggers an intense inflammatory reaction that clears the wound from dead cells and matrix debris, while activating a reparative program. A growing body of evidence suggests that members of the transforming growth factor (TGF)-β family critically regulate the inflammatory and reparative response following infarction. Although all three TGF-β isoforms (TGF-β1, -β2 and -β3) are markedly upregulated in the infarcted myocardium, information on isoform-specific actions is limited. Experimental studies have suggested that TGF-β exerts a wide range of actions on cardiomyocytes, fibroblasts, immune cells, and vascular cells. The findings are often conflicting, reflecting the contextdependence of TGF-β-mediated effects; conclusions are often based exclusively on in vitro studies and on associative evidence. TGF-β has been reported to modulate cardiomyocyte survival responses, promote monocyte recruitment, inhibit macrophage pro-inflammatory gene expression, suppress adhesion molecule synthesis by endothelial cells, promote myofibroblast conversion and extracellular matrix synthesis, and mediate both angiogenic and angiostatic effects. This review manuscript discusses our understanding of the cell biological effects of TGF-β in myocardial infarction. We discuss the relative significance of downstream TGF-β-mediated Smad-dependent and -independent pathways, and the risks and challenges of therapeutic TGF-β targeting. Considering the high significance of TGF-β-mediated actions in vivo, study of cell-specific effects and dissection of downstream signaling pathways are needed in order to design safe and effective therapeutic approaches.

AB - The adult mammalian heart has negligible regenerative capacity. Following myocardial infarction, sudden necrosis of cardiomyocytes triggers an intense inflammatory reaction that clears the wound from dead cells and matrix debris, while activating a reparative program. A growing body of evidence suggests that members of the transforming growth factor (TGF)-β family critically regulate the inflammatory and reparative response following infarction. Although all three TGF-β isoforms (TGF-β1, -β2 and -β3) are markedly upregulated in the infarcted myocardium, information on isoform-specific actions is limited. Experimental studies have suggested that TGF-β exerts a wide range of actions on cardiomyocytes, fibroblasts, immune cells, and vascular cells. The findings are often conflicting, reflecting the contextdependence of TGF-β-mediated effects; conclusions are often based exclusively on in vitro studies and on associative evidence. TGF-β has been reported to modulate cardiomyocyte survival responses, promote monocyte recruitment, inhibit macrophage pro-inflammatory gene expression, suppress adhesion molecule synthesis by endothelial cells, promote myofibroblast conversion and extracellular matrix synthesis, and mediate both angiogenic and angiostatic effects. This review manuscript discusses our understanding of the cell biological effects of TGF-β in myocardial infarction. We discuss the relative significance of downstream TGF-β-mediated Smad-dependent and -independent pathways, and the risks and challenges of therapeutic TGF-β targeting. Considering the high significance of TGF-β-mediated actions in vivo, study of cell-specific effects and dissection of downstream signaling pathways are needed in order to design safe and effective therapeutic approaches.

KW - Cardiac remodeling

KW - Cardiomyocyte

KW - Fibroblast

KW - Inflammation

KW - Myocardial infarction

KW - Transforming growth factor-beta (TGF-β)

UR - http://www.scopus.com/inward/record.url?scp=85016446747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016446747&partnerID=8YFLogxK

U2 - 10.21037/jtd.2016.11.19

DO - 10.21037/jtd.2016.11.19

M3 - Review article

AN - SCOPUS:85016446747

VL - 9

SP - S52-S63

JO - Journal of Thoracic Disease

JF - Journal of Thoracic Disease

SN - 2072-1439

ER -