ArticleNature communications2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- HDAC3 mediates retinal endothelial cell metabolic reprogramming and angiogenesis.Acta pharmacologica Sinica · 2026Article
- An atlas of cGAS-STING signaling in pathophysiological angiogenesis and retinal vascular homeostasis across species.Molecular therapy. Nucleic acids · 2026Article
- RNA-seq analysis reveals altered gene expression profiles in HMEC-1 cells overexpressing KRAS gene associated with brain arteriovenous malformation.Chinese neurosurgical journal · 2026Article
- Stress-induced mitochondrial fragmentation in endothelial cells disrupts blood-retinal barrier integrity causing neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Endothelial GTPBP3 directs developmental angiogenesis and neovascularization after limb ischemia via the mtROS/HRl/ATF4/mTORC1 axis.Angiogenesis · 2025Article
- Single-cell transcriptome profiling reveals dynamic cell populations and immune infiltration in cerebral cavernous malformation.Frontiers in immunology · 2025Article
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- Mitochondrial control of hypoxia-induced pathological retinal angiogenesis.Angiogenesis · 2024Article
- mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.Circulation research · 2024Article
- Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro.Prostaglandins, leukotrienes, and essential fatty acids · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Although mitochondrial activity is critical for angiogenesis, its mechanism is not entirely clear. Here we show that mice with endothelial deficiency of any one of the three nuclear genes encoding for mitochondrial proteins, transcriptional factor (TFAM), respiratory complex IV component (COX10), or redox protein thioredoxin 2 (TRX2), exhibit retarded retinal vessel growth and arteriovenous malformations (AVM). Single-cell RNA-seq analyses indicate that retinal ECs from the three mutant mice have increased TGFβ signaling and altered gene expressions associated with vascular maturation and extracellular matrix, correlating with vascular malformation and increased basement membrane thickening in microvesels of mutant retinas. Mechanistic studies suggest that mitochondrial dysfunction from Tfam, Cox10, or Trx2 depletion induces a mitochondrial localization and MAPKs-mediated phosphorylation of SMAD2, leading to enhanced ALK5-SMAD2 signaling. Importantly, pharmacological blockade of ALK5 signaling or genetic deficiency of SMAD2 prevented retinal vessel growth retardation and AVM in all three mutant mice. Our studies uncover a novel mechanism whereby mitochondrial dysfunction via the ALK5-SMAD2 signaling induces retinal vascular malformations, and have therapeutic values for the alleviation of angiogenesis-associated human retinal diseases.
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