ArticleeLife2016
Mechanistic insights into a TIMP3-sensitive pathway constitutively engaged in the regulation of cerebral hemodynamics.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Contribution of "Omic" Studies to the Understanding of Cadasil. A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Systems biology analysis of vasodynamics in mouse cerebral arterioles during resting state and functional hyperemia.PLoS computational biology · 2026Article
- Brain Capillary Ion Channels: Physiology and Channelopathies.Physiology (Bethesda, Md.) · 2026Review
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- The Pathobiology of Cerebrovascular Lesions in CADASIL Small Vessel Disease.Basic & clinical pharmacology & toxicology · 2025Review
- Article
- Statistical analysis supports pervasive RNA subcellular localization and alternative 3' UTR regulation.eLife · 2024Article
- CADASIL: A NOTCH3-associated cerebral small vessel disease.Journal of advanced research · 2024Review
- Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow.Nature communications · 2024Article
- Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.The Journal of clinical investigation · 2024Review
- Causation in neuroscience: keeping mechanism meaningful.Nature reviews. Neuroscience · 2024Review
- Epidermal Growth Factor Receptors in Vascular Endothelial Cells Contribute to Functional Hyperemia in the Brain.International journal of molecular sciences · 2023Article
- Elevated TGFβ signaling contributes to cerebral small vessel disease in mouse models of Gould syndrome.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- The emerging role of the HTRA1 protease in brain microvascular disease.Frontiers in dementia · 2023Review
- Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Journal of biomedical research · 2022Article
- CADASIL mutations sensitize the brain to ischemia via spreading depolarizations and abnormal extracellular potassium homeostasis.The Journal of clinical investigation · 2022Article
- Tissue Inhibitor of Metalloproteases 3 (TIMP-3): In Vivo Analysis Underpins Its Role as a Master Regulator of Ectodomain Shedding.Membranes · 2022Review
- Proteomic profiling in cerebral amyloid angiopathy reveals an overlap with CADASIL highlighting accumulation of HTRA1 and its substrates.Acta neuropathologica communications · 2022Article
- Evaluating the Causal Effects of TIMP-3 on Ischaemic Stroke and Intracerebral Haemorrhage: A Mendelian Randomization Study.Frontiers in genetics · 2022Article
- Cognition, mood and behavior in CADASIL.Cerebral circulation - cognition and behavior · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
Cerebral small vessel disease (SVD) is a leading cause of stroke and dementia. CADASIL, an inherited SVD, alters cerebral artery function, compromising blood flow to the working brain. TIMP3 (tissue inhibitor of metalloproteinase 3) accumulation in the vascular extracellular matrix in CADASIL is a key contributor to cerebrovascular dysfunction. However, the linkage between elevated TIMP3 and compromised cerebral blood flow (CBF) remains unknown. Here, we show that TIMP3 acts through inhibition of the metalloprotease ADAM17 and HB-EGF to regulate cerebral arterial tone and blood flow responses. In a clinically relevant CADASIL mouse model, we show that exogenous ADAM17 or HB-EGF restores cerebral arterial tone and blood flow responses, and identify upregulated voltage-dependent potassium channel (KV) number in cerebral arterial myocytes as a heretofore-unrecognized downstream effector of TIMP3-induced deficits. These results support the concept that the balance of TIMP3 and ADAM17 activity modulates CBF through regulation of myocyte KV channel number.
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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.