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.
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.
Authors: Yajaira Suárez; Carlos Fernández-Hernando; Jun Yu; Scott A Gerber; Kenneth D Harrison; Jordan S Pober; M Luisa Iruela-Arispe; Matthias Merkenschlager; William C Sessa Journal: Proc Natl Acad Sci U S A Date: 2008-09-08 Impact factor: 11.205
Authors: Paula A da Costa Martins; Meriem Bourajjaj; Monika Gladka; Mara Kortland; Ralph J van Oort; Yigal M Pinto; Jeffery D Molkentin; Leon J De Windt Journal: Circulation Date: 2008-09-22 Impact factor: 29.690
Authors: Jian-Fu Chen; Elizabeth P Murchison; Ruhang Tang; Thomas E Callis; Mariko Tatsuguchi; Zhongliang Deng; Mauricio Rojas; Scott M Hammond; Michael D Schneider; Craig H Selzman; Gerhard Meissner; Cam Patterson; Gregory J Hannon; Da-Zhi Wang Journal: Proc Natl Acad Sci U S A Date: 2008-02-06 Impact factor: 11.205
Authors: Nora E Renthal; Chien-Cheng Chen; Koriand'r C Williams; Robert D Gerard; Janine Prange-Kiel; Carole R Mendelson Journal: Proc Natl Acad Sci U S A Date: 2010-11-15 Impact factor: 11.205
Authors: Robert A McDonald; Akiko Hata; Margaret R MacLean; Nicholas W Morrell; Andrew H Baker Journal: Cardiovasc Res Date: 2011-11-07 Impact factor: 10.787
Authors: Tran Thi Hien; Karolina M Turczyńska; Diana Dahan; Mari Ekman; Mario Grossi; Johan Sjögren; Johan Nilsson; Thomas Braun; Thomas Boettger; Eliana Garcia-Vaz; Karin Stenkula; Karl Swärd; Maria F Gomez; Sebastian Albinsson Journal: J Biol Chem Date: 2015-12-18 Impact factor: 5.157