ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2019
IGF-1 Deficiency Promotes Pathological Remodeling of Cerebral Arteries: A Potential Mechanism Contributing to the Pathogenesis of Intracerebral Hemorrhages in Aging.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Irradiation-induced brain senescence accelerates cardiac aging via systemic mechanisms: insights from transcriptomic profiling.GeroScience · 2026Article
- Canonical and emerging regulatory mechanisms of tissue remodeling: shared principles across organs and therapeutic opportunities.Frontiers in immunology · 2026Review
- Reduced IGF-1 signaling fails to limit Alzheimer's disease progression in a novel rat model of IGF-1R haploinsufficiency.Scientific reports · 2025Article
- Navigating anterior pituitary dysfunction after traumatic brain injury: mechanisms, diagnosis, and management.Acta neurologica Belgica · 2025Review
- Intracerebral Hemorrhage in Aging: Pathophysiology, Clinical Challenges, and Future Directions.Life (Basel, Switzerland) · 2025Review
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Bioinformatics analysis reveals major hub genes involved with extracellular matrix and inflammatory and endocrine pathways associated with intracranial aneurysm tissue.Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences · 2025Article
- Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.Journal of Alzheimer's disease : JAD · 2025Article
- Review
- Novel intravital approaches to quantify deep vascular structure and perfusion in the aging mouse brain using ultrasound localization microscopy (ULM).Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects.GeroScience · 2024Article
- Endothelial deficiency of insulin-like growth factor-1 receptor leads to blood-brain barrier disruption and accelerated endothelial senescence in mice, mimicking aspects of the brain aging phenotype.Microcirculation (New York, N.Y. : 1994) · 2024Article
- Microvascular smooth muscle cells exhibit divergent phenotypic switching responses to platelet-derived growth factor and insulin-like growth factor 1.Microvascular research · 2024Article
- IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice.Frontiers in aging neuroscience · 2024Article
- Acute neuroendocrine changes after traumatic brain injury.Brain & spine · 2024Review
- The Role of Methionine-Rich Diet in Unhealthy Cerebrovascular and Brain Aging: Mechanisms and Implications for Cognitive Impairment.Nutrients · 2023Review
- A framework of biomarkers for vascular aging: a consensus statement by the Aging Biomarker Consortium.Life medicine · 2023Article
- Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis.Frontiers in endocrinology · 2023Review
- Relationship between insulin-like growth factor-1 and cerebral small vessel disease and its mechanisms: advances in the field.Frontiers in aging neuroscience · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Clinical and experimental studies show that age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels promotes the pathogenesis of intracerebral hemorrhages, which critically contribute to the development of vascular cognitive impairment and disability in older adults. Yet, the mechanisms by which IGF-1 deficiency compromises structural integrity of the cerebral vasculature are not completely understood. To determine the role of IGF-1 deficiency in pathological remodeling of middle cerebral arteries (MCAs), we compared alterations in vascular mechanics, morphology, and remodeling-related gene expression profile in mice with liver-specific knockdown of IGF-1 (Igf1f/f + TBG-Cre-AAV8) and control mice with or without hypertension induced by angiotensin-II treatment. We found that IGF-1 deficiency resulted in thinning of the media and decreased wall-to-lumen ratio in MCAs. MCAs of control mice exhibited structural adaptation to hypertension, manifested as a significant increase in wall thickness, vascular smooth muscle cell (VSMC) hypertrophy, decreased internal diameter and up-regulation of extracellular matrix (ECM)-related genes. IGF-1 deficiency impaired hypertension-induced adaptive media hypertrophy and dysregulated ECM remodeling, decreasing elastin content and attenuating adaptive changes in ECM-related gene expression. Thus, circulating IGF-1 plays a critical role in maintenance of the structural integrity of cerebral arteries. Alterations of VSMC phenotype and pathological remodeling of the arterial wall associated with age-related IGF-1 deficiency have important translational relevance for the pathogenesis of intracerebral hemorrhages and vascular cognitive impairment in elderly hypertensive patients.
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