Details

Autor(en) / Beteiligte

• Fulop, Gabor A
• Ramirez-Perez, Francisco I
• Kiss, Tamas
• Tarantini, Stefano
• Valcarcel Ares, Marta Noa
• Toth, Peter
• Yabluchanskiy, Andriy
• Conley, Shannon M
• Ballabh, Praveen
• Martinez-Lemus, Luis A
• Ungvari, Zoltan
• Csiszar, Anna

Titel

IGF-1 Deficiency Promotes Pathological Remodeling of Cerebral Arteries: A Potential Mechanism Contributing to the Pathogenesis of Intracerebral Hemorrhages in Aging

Ist Teil von

• The journals of gerontology. Series A, Biological sciences and medical sciences, 2019-03, Vol.74 (4), p.446-454

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2019

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.