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.

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Albinsson, Sebastian ; Suarez, Yajaira ; Skoura, Athanasia ; Offermanns, Stefan ; Miano, Joseph M ; Sessa, William C. / MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. In: Arteriosclerosis, Thrombosis and Vascular Biology. 2010 ; Vol. 30, No. 6. pp. 1118-26.

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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 -