ArticleCirculation2015
Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention.
Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
94 citing papers in PubMed, 144 citations in OpenAlex.
- Distinct Multiomic Signatures of Environmental Exposure Drive Immune Dysregulation and Disease Activity in Early Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Ryanodine receptor cluster remodeling linksbioRxiv : the preprint server for biology · 2026Article
- NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson's disease.Cell genomics · 2026Article
- Late Cognitive or Mood Alterations With 'Status Cribrosum' and Diffuse White Matter Lesions: A New Cerebral Small Vessel Disease Phenotype Associated With Rare COL4A1 Variants Located Within Exon 23.European journal of neurology · 2026Article
- Glycocalyx and basal lamina in neurological disorders.Matrix biology : journal of the International Society for Matrix Biology · 2026Review
- Review
- Vascular contribution to cognitive impairment and dementia (VCID): proceedings of 2025 workshop of the Jackson Laboratory.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- GlialeLife · 2026Article
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- 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
- Neurotrauma induced retinal basement membrane COL4A1 defects are restored by adipose tissue derived mesenchymal stem cell concentrated conditioned medium.Stem cell research & therapy · 2025Article
- Anti-swelling and self-activating artificial proteoglycan assemblies as cartilaginous implant for post-microfracture healing.Nature communications · 2025Article
- Collagen IV in Gould syndrome and Alport syndrome.Nature reviews. Nephrology · 2025Review
- Basement membrane structure and function: Relating biology to mechanics.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- 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
- Conjugated therapy with coaxially printed neural stem cell-laden microfibers and umbilical cord mesenchymal stem cell derived exosomes on complete transactional spinal cord defects.Materials today. Bio · 2025Article
- The Pathobiology of Cerebrovascular Lesions in CADASIL Small Vessel Disease.Basic & clinical pharmacology & toxicology · 2025Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundCollagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) form heterotrimers critical for vascular basement membrane stability and function. Patients with COL4A1 or COL4A2 mutations suffer from diverse cerebrovascular diseases, including cerebral microbleeds, porencephaly, and fatal intracerebral hemorrhage (ICH). However, the pathogenic mechanisms remain unknown, and there is a lack of effective treatment. METHODS AND
resultsUsing Col4a1 and Col4a2 mutant mouse models, we investigated the genetic complexity and cellular mechanisms underlying the disease. We found that Col4a1 mutations cause abnormal vascular development, which triggers small-vessel disease, recurrent hemorrhagic strokes, and age-related macroangiopathy. We showed that allelic heterogeneity, genetic context, and environmental factors such as intense exercise or anticoagulant medication modulated disease severity and contributed to phenotypic heterogeneity. We found that intracellular accumulation of mutant collagen in vascular endothelial cells and pericytes was a key triggering factor of ICH. Finally, we showed that treatment of mutant mice with a US Food and Drug Administration-approved chemical chaperone resulted in a decreased collagen intracellular accumulation and a significant reduction in ICH severity.
conclusionsOur data are the first to show therapeutic prevention in vivo of ICH resulting from Col4a1 mutation and imply that a mechanism-based therapy promoting protein folding might also prevent ICH in patients with COL4A1 and COL4A2 mutations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.