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  1. Article ; Online: Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects.

    Miller, Lauren R / Bickel, Marisa A / Vance, Michaela L / Vaden, Hannah / Nagykaldi, Domonkos / Nyul-Toth, Adam / Bullen, Elizabeth C / Gautam, Tripti / Tarantini, Stefano / Yabluchanskiy, Andriy / Kiss, Tamas / Ungvari, Zoltan / Conley, Shannon M

    GeroScience

    2024  Volume 46, Issue 3, Page(s) 3481–3501

    Abstract: Cerebrovascular fragility and cerebral microhemorrhages (CMH) contribute to age-related cognitive impairment, mobility defects, and vascular cognitive impairment and dementia, impairing healthspan and reducing quality of life in the elderly. Insulin-like ...

    Abstract Cerebrovascular fragility and cerebral microhemorrhages (CMH) contribute to age-related cognitive impairment, mobility defects, and vascular cognitive impairment and dementia, impairing healthspan and reducing quality of life in the elderly. Insulin-like growth factor 1 (IGF-1) is a key vasoprotective growth factor that is reduced during aging. Circulating IGF-1 deficiency leads to the development of CMH and other signs of cerebrovascular dysfunction. Here our goal was to understand the contribution of IGF-1 signaling on vascular smooth muscle cells (VSMCs) to the development of CMH and associated gait defects. We used an inducible VSMC-specific promoter and an IGF-1 receptor (Igf1r) floxed mouse line (Myh11-Cre
    MeSH term(s) Aged ; Animals ; Humans ; Mice ; Gait ; Hypertension/genetics ; Hypertension/complications ; Insulin-Like Growth Factor I/metabolism ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/pathology ; Receptor, IGF Type 1/genetics ; Gait Disorders, Neurologic/genetics
    Chemical Substances Insulin-Like Growth Factor I (67763-96-6) ; Receptor, IGF Type 1 (EC 2.7.10.1) ; Igf1r protein, mouse
    Language English
    Publishing date 2024-02-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-024-01090-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article: IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice.

    Miller, Lauren R / Bickel, Marisa A / Tarantini, Stefano / Runion, Megan E / Matacchiera, Zoe / Vance, Michaela L / Hibbs, Clara / Vaden, Hannah / Nagykaldi, Domonkos / Martin, Teryn / Bullen, Elizabeth C / Pinckard, Jessica / Kiss, Tamas / Howard, Eric W / Yabluchanskiy, Andriy / Conley, Shannon M

    Frontiers in aging neuroscience

    2024  Volume 16, Page(s) 1320808

    Abstract: Introduction: Cerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during ... ...

    Abstract Introduction: Cerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during aging. Decreased circulating IGF-1 in animal models leads to the development of VCID-like symptoms, but the cellular mechanisms underlying IGF-1-deficiency associated pathologies in the aged cerebrovasculature remain poorly understood. Here, we test the hypothesis that vascular smooth muscle cells (VSMCs) play an integral part in mediating the vasoprotective effects of IGF-1.
    Methods: We used a hypertension-based model of cerebrovascular dysfunction in mice with VSMC-specific IGF-1 receptor (
    Results: VSMC-specific
    Discussion: These studies suggest that VSMCs are key targets for IGF-1 in the context of cerebrovascular health, playing a role in vessel stability alongside other cells in the neurovascular unit, and that VSMC dysfunction in aging likely contributes to VCID.
    Language English
    Publishing date 2024-02-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2024.1320808
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Increased Susceptibility to Cerebral Microhemorrhages Is Associated With Imaging Signs of Microvascular Degeneration in the Retina in an Insulin-Like Growth Factor 1 Deficient Mouse Model of Accelerated Aging.

    Miller, Lauren R / Tarantini, Stefano / Nyúl-Tóth, Ádám / Johnston, Morgan P / Martin, Teryn / Bullen, Elizabeth C / Bickel, Marisa A / Sonntag, William E / Yabluchanskiy, Andriy / Csiszar, Anna / Ungvari, Zoltan I / Elliott, Michael H / Conley, Shannon M

    Frontiers in aging neuroscience

    2022  Volume 14, Page(s) 788296

    Abstract: Age-related cerebrovascular defects contribute to vascular cognitive impairment and dementia (VCID) as well as other forms of dementia. There has been great interest in developing biomarkers and other tools for studying cerebrovascular disease using more ...

    Abstract Age-related cerebrovascular defects contribute to vascular cognitive impairment and dementia (VCID) as well as other forms of dementia. There has been great interest in developing biomarkers and other tools for studying cerebrovascular disease using more easily accessible tissues outside the brain such as the retina. Decreased circulating insulin-like growth factor 1 (IGF-1) levels in aging are thought to contribute to the development of cerebrovascular impairment, a hypothesis that has been supported by the use of IGF-1 deficient animal models. Here we evaluate vascular and other retinal phenotypes in animals with circulating IGF-1 deficiency and ask whether the retina mimics common age-related vascular changes in the brain such as the development of microhemorrhages. Using a hypertension-induced model, we confirm that IGF-1 deficient mice exhibited worsened microhemorrhages than controls. The retinas of IGF-1 deficient animals do not exhibit microhemorrhages but do exhibit signs of vascular damage and retinal stress such as patterns of vascular constriction and Müller cell activation. These signs of retinal stress are not accompanied by retinal degeneration or impaired neuronal function. These data suggest that the role of IGF-1 in the retina is complex, and while IGF-1 deficiency leads to vascular defects in both the brain and the retina, not all brain pathologies are evident in the retina.
    Language English
    Publishing date 2022-03-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2022.788296
    Database MEDical Literature Analysis and Retrieval System OnLINE

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