RT info:eu-repo/semantics/article
T1 Regulation of smooth muscle dystrophin and synaptopodin 2 expression by actin polymerization and vascular injury
A1 Turczyńska, Karolina M.
A1 Swärd, Karl
A1 Thi Hien, Tran
A1 Wohlfahrt, Johan
A1 Mattisson, Ingrid Yao
A1 Ekman, Mari
A1 Nilsson, Johan
A1 Sjögren, Johan
A1 Murugesan, Vignesh
A1 Hultgårdh-Nilsson, Anna
A1 Cidad Velasco, María del Pilar
A1 Hellstrand, Per
A1 Pérez García, María Teresa
A1 Albinsson, Sebastian
K1 Angioplasty
K1 Angioplastia
K1 Gene expression
K1 Expresión génica
K1 Vascular diseases
K1 Enfermedades vasculares
K1 32 Ciencias Médicas
AB Objective: Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a rolein the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscleremains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and todemonstrate the role of these genes in the regulation of vascular smooth muscle phenotype.Approach and Results: Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide,and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknownactin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypicmodulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscleand their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A.Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured humanarteries. Finally, using a dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that these genesare involved in the regulation of smooth muscle differentiation and function.Conclusions: This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth musclefunction, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlledin this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation ofsmooth muscle cells.
PB American Heart Association
SN 1524-4636
YR 2015
FD 2015
LK http://uvadoc.uva.es/handle/10324/44592
UL http://uvadoc.uva.es/handle/10324/44592
LA eng
NO Arteriosclerosis, Thrombosis, and Vascular Biology, 2015, vol. 35, n. 6. p. 1489-1497
NO Producción Científica
DS UVaDOC
RD 01-jun-2024