Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGF beta expression

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http://hdl.handle.net/10138/236615

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Panahi , M , Mesri , N Y , Samuelsson , E-B , Coupland , K G , Forsell , C , Graff , C , Tikka , S , Winblad , B , Viitanen , M , Karlström , H , Sundström , E & Behbahani , H 2018 , ' Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGF beta expression ' , Journal of Cellular and Molecular Medicine , vol. 22 , no. 6 , pp. 3016-3024 . https://doi.org/10.1111/jcmm.13534

Title: Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGF beta expression
Author: Panahi, Mahmod; Mesri, Naeimeh Yousefi; Samuelsson, Eva-Britt; Coupland, Kirsten G.; Forsell, Charlotte; Graff, Caroline; Tikka, Saara; Winblad, Bengt; Viitanen, Matti; Karlström, Helena; Sundström, Erik; Behbahani, Homira
Contributor: University of Helsinki, Medicum
Date: 2018-06
Language: eng
Number of pages: 9
Belongs to series: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
URI: http://hdl.handle.net/10138/236615
Abstract: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial fatal progressive degenerative disorder. One of the pathological hallmarks of CADASIL is a dramatic reduction of vascular smooth muscle cells (VSMCs) in cerebral arteries. Using VSMCs from the vasculature of the human umbilical cord, placenta and cerebrum of CADASIL patients, we found that CADASIL VSMCs had a lower proliferation rate compared to control VSMCs. Exposure of control VSMCs and endothelial cells (ECs) to media derived from CADASIL VSMCs lowered the proliferation rate of all cells examined. By quantitative RT-PCR analysis, we observed increased Transforming growth factor-beta (TGF beta) gene expression in CADASIL VSMCs. Adding TGF beta-neutralizing antibody restored the proliferation rate of CADASIL VSMCs. We assessed proliferation differences in the presence or absence of TGF beta-neutralizing antibody in ECs co-cultured with VSMCs. ECs co-cultured with CADASIL VSMCs exhibited a lower proliferation rate than those co-cultured with control VSMCs, and neutralization of TGF beta normalized the proliferation rate of ECs co-cultured with CADASIL VSMCs. We suggest that increased TGF beta expression in CADASIL VSMCs is involved in the reduced VSMC proliferation in CADASIL and may play a role in situ in altered proliferation of neighbouring cells in the vasculature.
Subject: CADASIL
endothelial cells
NOTCH3
Transforming growth factor-beta
vascular smooth muscle cells
GROWTH-FACTOR-BETA
AUTOSOMAL-DOMINANT ARTERIOPATHY
SUBCORTICAL INFARCTS
WHITE-MATTER
ENDOTHELIAL-CELLS
BRAIN INFARCTS
MUTATIONS
LEUKOENCEPHALOPATHY
SPECTRUM
ENDOGLIN
3111 Biomedicine
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