ArticleThe Journal of clinical investigation2021
Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- Heterozygous HTRA1-related Cerebral Small Vessel Disease with Short Stature and Limbs.Internal medicine (Tokyo, Japan) · 2026Article
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- Neuroinflammation and blood-brain barrier dysfunction in cerebral small vessel disease: mechanisms, biomarkers, and therapeutic implications.European journal of medical research · 2026Review
- Rare Variants in HTRA1, SGTB, and RBM12 Confer Risk of Atherosclerotic Cardiovascular Disease Independent of Traditional Cardiovascular Risk Factors.Circulation. Genomic and precision medicine · 2025Article
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- Article
- "Chocolate Chip Sign" on Susceptibility-Weighted Imaging: A Novel Neuroimaging Biomarker for HTRA1-Related Cerebral Small Vessel Disease.Neurology. Genetics · 2025Article
- Monogenic causes of cerebral small vessel disease- models for vascular cognitive impairment and dementia?Current opinion in psychiatry · 2025Review
- A novel gene edited rat model of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).Cerebral circulation - cognition and behavior · 2025Article
- Bidirectional Crosstalk between the Heart and Brain in Alzheimer's Disease.Aging and disease · 2024Review
- Rational correction of pathogenic conformational defects in HTRA1.Nature communications · 2024Article
- Redefining common and rare HTRA1 variants as risk factors for polyvascular disease.Nature cardiovascular research · 2024Article
- Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.The Journal of clinical investigation · 2024Review
- Modeling of age-related neurological disease: utility of zebrafish.Frontiers in aging neuroscience · 2024Review
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease.Research square · 2023Article
- A brief overview of a mouse model of cerebral hypoperfusion by bilateral carotid artery stenosis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Role of cytokines and reactive oxygen species in brain aging.Mechanisms of ageing and development · 2023Review
- Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer's disease.Molecular neurodegeneration · 2023Review
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Authors and funding
30 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.
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