Perturbations of the cerebrovascular matrisome: A convergent mechanism in small vessel disease of the brain?
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ABSTRACT:
SUBMITTER: Joutel A
PROVIDER: S-EPMC4758555 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
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Perturbations of the cerebrovascular matrisome: A convergent mechanism in small vessel disease of the brain?
Joutel Anne A Haddad Iman I Ratelade Julien J Nelson Mark T MT
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20160101 1
The term matrisome refers to the ensemble of proteins constituting the extracellular matrix (ECM) (core matrisome) as well as the proteins associated with the ECM. Every organ has an ECM with a unique composition that not only provides the support and anchorage for cells, but also controls fundamental cellular processes as diverse as differentiation, survival, proliferation, and polarity. The current knowledge of the matrisome of small brain vessels is reviewed with a focus on the basement membr ...[more]
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Project description:Cerebral small vessel disease (cSVD) is the most common cause of vascular cognitive impairment and dementia (VCID) and highly associated with Alzheimer’s disease pathogenesis. There is an urgent need to establish relevant animal models for cSVD. As aging is the strongest risk factor for these diseases, cerebrovascular senescence is implicated in cSVD pathogenesis. We investigated how AAV-based expression of senescence marker CDKN2A/p16INK4A in cerebrovascular endothelial cells influences cSVD phenotypes in adult wild-type mice. A single intraperitoneal injection of the AAV carrying CDKN2A/p16INK4A caused blood-brain barrier impairments, neurovascular uncoupling, and reduction of cerebral blood flow, accompanied with behavioral changes in mice. While single cell RNA-sequencing and immunostaining revealed the upregulation of VCAM1 in cerebrovascular endothelial cells, in vivo two-photon excitation microscopy detected aggravated leukocyte adhesions to capillaries. Our findings demonstrate the contributions of p16INK4A in cerebrovascular endothelial cells to cSVD and VCID pathogenesis through new mouse model.
2025-08-20 | GSE304696 | GEO
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Project description:Cerebrovascular p16INK4A expression induces cerebral small vessel disease-related phenotypes
| PRJNA1302351 | ENA
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| S-EPMC6928551 | biostudies-literature