IGF-1 Deficiency Promotes Pathological Remodeling of Cerebral Arteries: A Potential Mechanism Contributing to the Pathogenesis of Intracerebral Hemorrhages in Aging.
Hypertension
IGF-1
Neuroendocrine aging
Remodeling
Vascular aging
Vascular smooth muscle cell
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
14 03 2019
14 03 2019
Historique:
received:
12
02
2018
pubmed:
23
6
2018
medline:
27
12
2019
entrez:
23
6
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 29931048
pii: 5042711
doi: 10.1093/gerona/gly144
pmc: PMC6417448
doi:
Substances chimiques
Angiotensin II
11128-99-7
Insulin-Like Growth Factor I
67763-96-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
446-454Subventions
Organisme : NIGMS NIH HHS
ID : U54 GM104938
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG050911
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG047879
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS056218
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG038747
Pays : United States
Organisme : NCCIH NIH HHS
ID : R01 AT006526
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG052363
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG055395
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL088105
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM125528
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS100782
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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