TY - JOUR
T1 - Role of angiogenic transdifferentiation in vascular recovery
AU - Cooke, John P.
AU - Lai, Li
N1 - Funding Information:
This work is supported in part by grants to JPC from the National Institutes of Health (NIH) R01s HL133254, HL157790, and HL148338; as well as the Cancer Prevention and Research Institute of Texas CPRIT RP150611). Our manuscript was graced by the artistry of Rachael Whitehead, who created the figure.
Publisher Copyright:
2023 Cooke and Lai.
PY - 2023
Y1 - 2023
N2 - Tissue repair requires the orchestration of multiple processes involving a multiplicity of cellular effectors, signaling pathways, and cell-cell communication. The regeneration of the vasculature is a critical process for tissue repair and involves angiogenesis, adult vasculogenesis, and often arteriogenesis, which processes enable recovery of perfusion to deliver oxygen and nutrients to the repair or rebuild of the tissue. Endothelial cells play a major role in angiogenesis, whereas circulating angiogenic cells (primarily of hematopoietic origin) participate in adult vasculogenesis, and monocytes/macrophages have a defining role in the vascular remodeling that is necessary for arteriogenesis. Tissue fibroblasts participate in tissue repair by proliferating and generating the extracellular matrix as the structural scaffold for tissue regeneration. Heretofore, fibroblasts were not generally believed to be involved in vascular regeneration. However, we provide new data indicating that fibroblasts may undergo angiogenic transdifferentiation, to directly expand the microvasculature. Transdifferentiation of fibroblasts to endothelial cells is initiated by inflammatory signaling which increases DNA accessibility and cellular plasticity. In the environment of under-perfused tissue, the activated fibroblasts with increased DNA accessibility can now respond to angiogenic cytokines, which provide the transcriptional direction to induce fibroblasts to become endothelial cells. Periphery artery disease (PAD) involves the dysregulation of vascular repair and inflammation. Understanding the relationship between inflammation, transdifferentiation, and vascular regeneration may lead to a new therapeutic approach to PAD.
AB - Tissue repair requires the orchestration of multiple processes involving a multiplicity of cellular effectors, signaling pathways, and cell-cell communication. The regeneration of the vasculature is a critical process for tissue repair and involves angiogenesis, adult vasculogenesis, and often arteriogenesis, which processes enable recovery of perfusion to deliver oxygen and nutrients to the repair or rebuild of the tissue. Endothelial cells play a major role in angiogenesis, whereas circulating angiogenic cells (primarily of hematopoietic origin) participate in adult vasculogenesis, and monocytes/macrophages have a defining role in the vascular remodeling that is necessary for arteriogenesis. Tissue fibroblasts participate in tissue repair by proliferating and generating the extracellular matrix as the structural scaffold for tissue regeneration. Heretofore, fibroblasts were not generally believed to be involved in vascular regeneration. However, we provide new data indicating that fibroblasts may undergo angiogenic transdifferentiation, to directly expand the microvasculature. Transdifferentiation of fibroblasts to endothelial cells is initiated by inflammatory signaling which increases DNA accessibility and cellular plasticity. In the environment of under-perfused tissue, the activated fibroblasts with increased DNA accessibility can now respond to angiogenic cytokines, which provide the transcriptional direction to induce fibroblasts to become endothelial cells. Periphery artery disease (PAD) involves the dysregulation of vascular repair and inflammation. Understanding the relationship between inflammation, transdifferentiation, and vascular regeneration may lead to a new therapeutic approach to PAD.
KW - angiogenesis
KW - endothelial cells
KW - fibroblasts
KW - nuclear reprogramming
KW - transflammation
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U2 - 10.3389/fcvm.2023.1155835
DO - 10.3389/fcvm.2023.1155835
M3 - Review article
C2 - 37200975
AN - SCOPUS:85159332819
SN - 2297-055X
VL - 10
SP - 1155835
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 1155835
ER -