ArticleEBioMedicine2024
Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Triglyceride Polygenic Score Identifies Individuals Who May Respond Differently to Aspirin in Primary Prevention.Clinical pharmacology and therapeutics · 2026Article
- Unwinding the Neurovascular Unit: The Vascular Extracellular Matrix and Mechanochemical Collagen Functionalization in Vascular Dementia.International journal of molecular sciences · 2026Review
- Age-dependent vascular and neurological characteristics of CADASIL are recapitulated in Notch3 mutant zebrafish, implicating a role for type IV collagen in disease progression.Acta neuropathologica communications · 2026Article
- Glycocalyx and basal lamina in neurological disorders.Matrix biology : journal of the International Society for Matrix Biology · 2026Review
- Genetics of intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Cerebral Small Vessel Disease and Blood-Brain Barrier Disruption: Mechanisms and Therapeutic Strategies in Cognitive Impairment.Translational stroke research · 2026Review
- Identification of a putative progenitor-like chondrocyte subpopulation in osteoarthritic human cartilage.Stem cell research & therapy · 2026Article
- Identification of COL4A2 as a Biomarker of Extracellular Matrix Remodeling and Vascular Scaffold in Choroid for Myopia.Investigative ophthalmology & visual science · 2026Article
- TWIST1 drives endothelial-to-mesenchymal-transition to stabilize atherosclerotic plaques.Nature communications · 2026Article
- Zebrafish col4a1 loss-of-function models mirror key neurovascular and ocular features of COL4A1/A2 syndrome and enable human variants assessment in vivo.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Late-onset intracerebral hemorrhage associated with COL4A1 variants: clinical and genetic perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Genetic and epigenetic architectures of stroke: Insights from GWAS to precision medicine.Neurochemistry international · 2025Review
- Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- A multifunction murine Col4a1 allele reveals potential gene therapy parameters for Gould syndrome.The Journal of cell biology · 2025Article
- Integrated machine learning and single-cell RNA sequencing reveal COL4A2 and CXCL6 as oxidative stress-associated biomarkers in periodontitis.Frontiers in immunology · 2025Article
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Authors and funding
29 authors.
Funding
Abstract
backgroundGenetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure.
methodsVascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH.
findingsCol4a1 missense mutations cause early-onset CSVD independent of hypertension, with enhanced vasodilation of small arteries due to endothelial dysfunction, vascular wall thickening and reduced stiffness. Mechanistically, the early-onset dysregulated endothelium-dependent hyperpolarization (EDH) is due to reduced collagen IV levels with elevated activity and levels of endothelial Ca
interpretationCOL4A1/COL4A2 variants act in genetic and sporadic CSVD with ICH via dysregulated EDH, and altered vascular wall thickness and biomechanics due to lower collagen IV levels and/or mutant collagen IV secretion. These data highlight EDH and collagen IV levels as potential treatment targets.
fundingMRC, Wellcome Trust, BHF.
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