Perspective: Pathological transdifferentiation—a novel therapeutic target for cardiovascular diseases and chronic inflammation DOI Creative Commons

William Y. Yang,

Melissa Mahgoub,

Fatma Saaoud

и другие.

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Ноя. 26, 2024

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 potential targeting in cardiovascular diseases chronic inflammation. Current therapies mainly focus on mitigating early inflammatory response through proinflammatory cytokines pathways targeting, including corticosteroids, TNF-α inhibitors, IL-1β monoclonal antibodies blockers, IL-6 nonsteroidal anti-inflammatory drugs (NSAIDs), along with modulating innate immune memory (trained immunity). However, these approaches often fail to address long-term tissue damage functional regeneration. For instance, fibroblasts can transdifferentiate myofibroblasts cardiac fibrosis, endothelial may undergo mesenchymal transition (EndMT) vascular remodeling, resulting fibrosis impaired function. Targeting pathological transdifferentiation promising therapeutic avenue by focusing key signaling drive aberrant cellular phenotypic transcriptomic transitions. approach seeks inhibit or modulate plasticity effective regeneration prevent fibrosis. Such strategies have the inflammation, death, damage, providing more comprehensive sustainable treatment solution. Future research should understanding mechanisms behind identifying relevant biomarkers master regulators, developing preclinical clinical trials. Integrating new existing treatments could enhance efficacy improve patient outcomes. Highlighting as target paradigms, leading better management recovery of tissues

Язык: Английский

Role of Trained Immunity in Heath and Disease DOI
Shibali Das, Kory J. Lavine

Current Cardiology Reports, Год журнала: 2025, Номер 27(1)

Опубликована: Янв. 13, 2025

Язык: Английский

Процитировано

0
Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model DOI

Fatma Saaoud,

Lu Liu,

Keman Xu

и другие.

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

Background Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment. Neuroinflammatory processes, mediated glial and immune cells, contribute to neuronal damage. Emerging evidence implicates innate mechanisms, including trained immunity cell trans-differentiation, in AD pathogenesis, though their roles remain unclear. Objective To investigate transcriptomic changes the 3xTg-AD mouse model, focusing on trans-differentiation mechanisms. Methods RNA-sequencing was performed brain tissue (cortex plus hippocampus) from 11-month-old female wild-type mice (n = 3/group). Differentially expressed genes (fold change > 1.5, p < 0.05) were identified followed bioinformatics knowledge-based profiling. Public datasets also analyzed. Results exhibited 316 upregulated 412 downregulated genes. Downregulated included those for blood-brain barrier protein, while related cerebrospinal fluid. Increased expression of proinflammatory markers, as well differentiation, proliferation, activation, adhesion. Upregulation associated with migration suggests potential role inflammation cellular plasticity. Additionally, involved inflammasome pathways, immunometabolism, upregulated. Mechanistically, these modulated knockdown promoter SET-7, overexpression inhibitor IL-37, knockout IL-1 receptor, caspase-1, pattern recognition receptor CD36. Conclusions The finding underscore AD, revealing mechanistic framework which danger-associated molecular patterns drive responses, plasticity offering therapeutic targets neuroinflammation reprograming.

Язык: Английский

Процитировано

0
Immune Checkpoints Are New Therapeutic Targets in Regulating Cardio-, and Cerebro-Vascular Diseases and CD4+Foxp3+ Regulatory T Cell Immunosuppression DOI Creative Commons
Ying Shao,

William Y. Yang,

Gayani Nanayakkara

и другие.

International Journal of Drug Discovery and Pharmacology, Год журнала: 2024, Номер unknown, С. 100022 - 100022

Опубликована: Ноя. 26, 2024

Although previous reviews explored the roles of selected immune checkpoints (ICPs) in cardiovascular diseases (CVD) and cerebrovascular from various perspectives, many related aspects have yet to be thoroughly reviewed analyzed. Our comprehensive review addresses this gap by discussing cellular functions ICPs, focusing on tissue-specific microenvironment-localized transcriptomic posttranslational regulation ICP expressions, as well their functional interactions with metabolic reprogramming. We also analyze how 14 pairs including CTLA-4/CD86-CD80, PD1-PDL-1, TIGIT-CD155, regulate CVD pathogenesis. Additionally, covers ICPs modulating CD4+Foxp3+ regulatory T cells (Tregs), cells, innate CVDs diseases. Furthermore, we outline seven immunological principles guide development new ICP-based therapies for CVDs. This timely thorough analysis recent advancements challenges provide insights into role CVDs, Tregs, will support novel therapeutics strategies these

Язык: Английский

Процитировано

2
Perspective: Pathological transdifferentiation—a novel therapeutic target for cardiovascular diseases and chronic inflammation DOI Creative Commons

William Y. Yang,

Melissa Mahgoub,

Fatma Saaoud

и другие.

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Ноя. 26, 2024

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 potential targeting in cardiovascular diseases chronic inflammation. Current therapies mainly focus on mitigating early inflammatory response through proinflammatory cytokines pathways targeting, including corticosteroids, TNF-α inhibitors, IL-1β monoclonal antibodies blockers, IL-6 nonsteroidal anti-inflammatory drugs (NSAIDs), along with modulating innate immune memory (trained immunity). However, these approaches often fail to address long-term tissue damage functional regeneration. For instance, fibroblasts can transdifferentiate myofibroblasts cardiac fibrosis, endothelial may undergo mesenchymal transition (EndMT) vascular remodeling, resulting fibrosis impaired function. Targeting pathological transdifferentiation promising therapeutic avenue by focusing key signaling drive aberrant cellular phenotypic transcriptomic transitions. approach seeks inhibit or modulate plasticity effective regeneration prevent fibrosis. Such strategies have the inflammation, death, damage, providing more comprehensive sustainable treatment solution. Future research should understanding mechanisms behind identifying relevant biomarkers master regulators, developing preclinical clinical trials. Integrating new existing treatments could enhance efficacy improve patient outcomes. Highlighting as target paradigms, leading better management recovery of tissues

Язык: Английский

Процитировано

0