TY  - JOUR
AU  - Ungvari, Z.
AU  - Tucsek, Zsuzsanna
AU  - Sosnowska, Danuta
AU  - Toth, Peter
AU  - Gautam, Tripti
AU  - Podlutsky, Andrej
AU  - Csiszar, Agnes
AU  - Losonczy, Gyorgy
AU  - Valcarcel-Ares, M Noa
AU  - Sonntag, William E
AU  - Csiszar, Anna
TI  - Aging-Induced Dysregulation of Dicer1-Dependent MicroRNA Expression Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells.
JO  - The journals of gerontology / A
VL  - 68
IS  - 8
SN  - 1758-535X
CY  - Oxford [u.a.]
PB  - Oxford Univ. Pr.
M1  - FZJ-2013-00514
SP  - 877-891
PY  - 2013
AB  - Age-related impairment of angiogenesis is likely to play a central role in cerebromicrovascular rarefaction and development of vascular cognitive impairment, but the underlying mechanisms remain elusive. To test the hypothesis that dysregulation of Dicer1 (ribonuclease III, a key enzyme of the microRNA [miRNA] machinery) impairs endothelial angiogenic capacity in aging, primary cerebromicrovascular endothelial cells (CMVECs) were isolated from young (3 months old) and aged (24 months old) Fischer 344 × Brown Norway rats. We found an age-related downregulation of Dicer1 expression both in CMVECs and in small cerebral vessels isolated from aged rats. In aged CMVECs, Dicer1 expression was increased by treatment with polyethylene glycol-catalase. Compared with young cells, aged CMVECs exhibited altered miRNA expression profile, which was associated with impaired proliferation, adhesion to vitronectin, collagen and fibronectin, cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing technology), and impaired ability to form capillary-like structures. Overexpression of Dicer1 in aged CMVECs partially restored miRNA expression profile and significantly improved angiogenic processes. In young CMVECs, downregulation of Dicer1 (siRNA) resulted in altered miRNA expression profile associated with impaired proliferation, adhesion, migration, and tube formation, mimicking the aging phenotype. Collectively, we found that Dicer1 is essential for normal endothelial angiogenic processes, suggesting that age-related dysregulation of Dicer1-dependent miRNA expression may be a potential mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging.
LB  - PUB:(DE-HGF)16
C6  - pmid:23239824
UR  - <Go to ISI:>//WOS:000322298700001
DO  - DOI:10.1093/gerona/gls242
UR  - https://juser.fz-juelich.de/record/128991
ER  -