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Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects.
- Source :
- GeroScience; Jun2024, Vol. 46 Issue 3, p3481-3501, 21p
- Publication Year :
- 2024
-
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<superscript>ERT2</superscript> Igf1r<superscript>f/f</superscript>) to knockdown Igf1r. Angiotensin II in combination with L-NAME-induced hypertension was used to elicit CMH. We observed that VSMC-specific Igf1r knockdown mice had accelerated development of CMH, and subsequent associated gait irregularities. These phenotypes were accompanied by upregulation of a cluster of pro-inflammatory genes associated with VSMC maladaptation. Collectively our findings support an essential role for VSMCs as a target for the vasoprotective effects of IGF-1, and suggest that VSMC dysfunction in aging may contribute to the development of CMH. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 25092715
- Volume :
- 46
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- GeroScience
- Publication Type :
- Academic Journal
- Accession number :
- 178047170
- Full Text :
- https://doi.org/10.1007/s11357-024-01090-7