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IGF‐1 deficiency promotes pathological remodeling of cerebral arteries: a potential mechanism contributing to the pathogenesis of intracerebral hemorrhages in aging
Author(s) -
Fulop Gabor A.,
RamirezPerez Francisco I.,
Kiss Tamas,
Tarantini Stefano,
Toth Peter,
Yabluchanskiy Andriy,
Conley Shan M.,
Ballabh Praveen,
MartinezLemus Luis A.,
Ungvari Zoltan,
Csiszar Anna
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.711.8
Subject(s) - pathogenesis , muscle hypertrophy , medicine , vascular remodelling in the embryo , pathological , extracellular matrix , cerebral arteries , elastin , endocrinology , pathology , biology , microbiology and biotechnology
Clinical and experimental studies show that age‐related decline in circulating 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 ( Igf1 f/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 hypertrophy, decreased internal diameter and up‐regulation of extracellular matrix (ECM)‐related genes. IGF‐1 deficiency impaired hypertension‐induced adaptive media hypertrophy and dysregulated extracellular matrix 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 ICHs and vascular cognitive impairment in elderly hypertensive patients. Support or Funding Information This work was supported by grants from the American Heart Association, the National Center for Complementary and Alternative Medicine, and the National Institute on Aging This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .