TY - JOUR
T1 - Perspective
T2 - Pathological transdifferentiation—a novel therapeutic target for cardiovascular diseases and chronic inflammation
AU - Yang, William Y.
AU - Ben Issa, Mohammed
AU - Saaoud, Fatma
AU - Xu, Keman
AU - Shao, Ying
AU - Lu, Yifan
AU - Dornas, Waleska
AU - Cueto, Ramon
AU - Jiang, Xiaohua
AU - Wang, Hong
AU - Yang, Xiaofeng
N1 - © 2024 Yang, Ben Issa, Saaoud, Xu, Shao, Lu, Dornas, Cueto, Jiang, Wang and Yang.
PY - 2024
Y1 - 2024
N2 - Pathological transdifferentiation, where differentiated cells aberrantly transform into other cell types that exacerbate disease rather than promote healing, represents a novel and significant concept. This perspective discusses its role and potential targeting in cardiovascular diseases and chronic inflammation. Current therapies mainly focus on mitigating early inflammatory response through proinflammatory cytokines and pathways targeting, including corticosteroids, TNF-α inhibitors, IL-1β monoclonal antibodies and blockers, IL-6 blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs), along with modulating innate immune memory (trained immunity). However, these approaches often fail to address long-term tissue damage and functional regeneration. For instance, fibroblasts can transdifferentiate into myofibroblasts in cardiac fibrosis, and endothelial cells may undergo endothelial to mesenchymal transition (EndMT) in vascular remodeling, resulting in fibrosis and impaired tissue function. Targeting pathological transdifferentiation represents a promising therapeutic avenue by focusing on key signaling pathways that drive these aberrant cellular phenotypic and transcriptomic transitions. This approach seeks to inhibit these pathways or modulate cellular plasticity to promote effective tissue regeneration and prevent fibrosis. Such strategies have the potential to address inflammation, cell death, and the resulting tissue damage, providing a more comprehensive and sustainable treatment solution. Future research should focus on understanding the mechanisms behind pathological transdifferentiation, identifying relevant biomarkers and master regulators, and developing novel therapies through preclinical and clinical trials. Integrating these new therapies with existing anti-inflammatory treatments could enhance efficacy and improve patient outcomes. Highlighting pathological transdifferentiation as a therapeutic target could transform treatment paradigms, leading to better management and functional recovery of cardiovascular tissues in diseases and chronic inflammation.
AB - Pathological transdifferentiation, where differentiated cells aberrantly transform into other cell types that exacerbate disease rather than promote healing, represents a novel and significant concept. This perspective discusses its role and potential targeting in cardiovascular diseases and chronic inflammation. Current therapies mainly focus on mitigating early inflammatory response through proinflammatory cytokines and pathways targeting, including corticosteroids, TNF-α inhibitors, IL-1β monoclonal antibodies and blockers, IL-6 blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs), along with modulating innate immune memory (trained immunity). However, these approaches often fail to address long-term tissue damage and functional regeneration. For instance, fibroblasts can transdifferentiate into myofibroblasts in cardiac fibrosis, and endothelial cells may undergo endothelial to mesenchymal transition (EndMT) in vascular remodeling, resulting in fibrosis and impaired tissue function. Targeting pathological transdifferentiation represents a promising therapeutic avenue by focusing on key signaling pathways that drive these aberrant cellular phenotypic and transcriptomic transitions. This approach seeks to inhibit these pathways or modulate cellular plasticity to promote effective tissue regeneration and prevent fibrosis. Such strategies have the potential to address inflammation, cell death, and the resulting tissue damage, providing a more comprehensive and sustainable treatment solution. Future research should focus on understanding the mechanisms behind pathological transdifferentiation, identifying relevant biomarkers and master regulators, and developing novel therapies through preclinical and clinical trials. Integrating these new therapies with existing anti-inflammatory treatments could enhance efficacy and improve patient outcomes. Highlighting pathological transdifferentiation as a therapeutic target could transform treatment paradigms, leading to better management and functional recovery of cardiovascular tissues in diseases and chronic inflammation.
KW - cardiovascular diseases
KW - chronic inflammation
KW - endothelial to mesenchymal transition
KW - epithelial to mesenchymal transition
KW - pathological transdifferentiation
KW - vascular smooth muscle to mesenchymal transition
UR - http://www.scopus.com/inward/record.url?scp=85211641979&partnerID=8YFLogxK
U2 - 10.3389/fcvm.2024.1500775
DO - 10.3389/fcvm.2024.1500775
M3 - Article
C2 - 39660114
AN - SCOPUS:85211641979
SN - 2297-055X
VL - 11
SP - 1500775
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 1500775
ER -