MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function
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MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. / Albinsson, Sebastian; Suarez, Yajaira; Skoura, Athanasia; Offermanns, Stefan; Miano, Joseph M; Sessa, William C.
In: Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 30, No. 6, 06.2010, p. 1118-26.Research output: Contribution to journal › Article
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TY - JOUR
T1 - MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function
AU - Albinsson, Sebastian
AU - Suarez, Yajaira
AU - Skoura, Athanasia
AU - Offermanns, Stefan
AU - Miano, Joseph M
AU - Sessa, William C
PY - 2010/6
Y1 - 2010/6
N2 - OBJECTIVE: Regulation of vascular smooth muscle (VSM) proliferation and contractile differentiation is an important factor in vascular development and subsequent cardiovascular diseases. Recently, microRNAs (miRNAs) have been shown to regulate fundamental cellular processes in a number of cell types, but the integrated role of miRNAs in VSM in blood vessels is unknown. Here, we investigated the role of miRNAs in VSM by deleting the rate-limiting enzyme in miRNA synthesis, Dicer.METHODS AND RESULTS: Deletion of Dicer in VSM results in late embryonic lethality at embryonic day 16 to 17, associated with extensive internal hemorrhage. The loss of VSM Dicer results in dilated, thin-walled blood vessels caused by a reduction in cellular proliferation. In addition, blood vessels from VSM-deleted Dicer mice exhibited impaired contractility because of a loss of contractile protein markers. We found this effect to be associated with a loss of actin stress fibers and partly rescued by overexpression of microRNA (miR)-145 or myocardin.CONCLUSIONS: Dicer-dependent miRNAs are important for VSM development and function by regulating proliferation and contractile differentiation.
AB - OBJECTIVE: Regulation of vascular smooth muscle (VSM) proliferation and contractile differentiation is an important factor in vascular development and subsequent cardiovascular diseases. Recently, microRNAs (miRNAs) have been shown to regulate fundamental cellular processes in a number of cell types, but the integrated role of miRNAs in VSM in blood vessels is unknown. Here, we investigated the role of miRNAs in VSM by deleting the rate-limiting enzyme in miRNA synthesis, Dicer.METHODS AND RESULTS: Deletion of Dicer in VSM results in late embryonic lethality at embryonic day 16 to 17, associated with extensive internal hemorrhage. The loss of VSM Dicer results in dilated, thin-walled blood vessels caused by a reduction in cellular proliferation. In addition, blood vessels from VSM-deleted Dicer mice exhibited impaired contractility because of a loss of contractile protein markers. We found this effect to be associated with a loss of actin stress fibers and partly rescued by overexpression of microRNA (miR)-145 or myocardin.CONCLUSIONS: Dicer-dependent miRNAs are important for VSM development and function by regulating proliferation and contractile differentiation.
KW - Actins
KW - Animals
KW - Aorta
KW - Cell Differentiation
KW - Cell Proliferation
KW - Cells, Cultured
KW - DEAD-box RNA Helicases
KW - Embryo Loss
KW - Endoribonucleases
KW - Gene Expression Regulation, Developmental
KW - Genotype
KW - Gestational Age
KW - Hemorrhage
KW - Integrases
KW - Liver Diseases
KW - Male
KW - Mice
KW - Mice, Knockout
KW - MicroRNAs
KW - Microfilament Proteins
KW - Muscle Development
KW - Muscle Proteins
KW - Muscle, Smooth, Vascular
KW - Nuclear Proteins
KW - Phenotype
KW - Ribonuclease III
KW - Stress Fibers
KW - Trans-Activators
KW - Transcriptional Activation
KW - Transfection
KW - Umbilical Arteries
KW - Vasoconstriction
KW - Vasodilation
U2 - 10.1161/ATVBAHA.109.200873
DO - 10.1161/ATVBAHA.109.200873
M3 - Article
C2 - 20378849
VL - 30
SP - 1118
EP - 1126
JO - Arteriosclerosis, Thrombosis and Vascular Biology
JF - Arteriosclerosis, Thrombosis and Vascular Biology
SN - 1524-4636
IS - 6
ER -