MicroRNAs Are Necessary for Vascular Smooth Muscle Growth, Differentiation, and Function

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2010 Apr 10

PMID 20378849

Citations 137

Authors

Sebastian Albinsson

Yajaira Suarez

Athanasia Skoura

Stefan Offermanns

Joseph M Miano

William C Sessa

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Harnessing the power of miRNAs for precision diagnosis and treatment of male infertility.

Doghish A, Elsakka E, Ahmed Mohamed Moustafa H, Ashraf A, Mageed S, Mohammed O Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39535597 DOI: 10.1007/s00210-024-03594-7.

Treatment of erectile dysfunction by intracavernosal administration of mesenchymal stem cells in patients with diabetes mellitus.

Iskakov Y, Omarbayev R, Nugumanov R, Turgunbayev T, Yermaganbetov Y Int Braz J Urol. 2024; 50(4):386-397.

PMID: 38701187 PMC: 11262727. DOI: 10.1590/S1677-5538.IBJU.2024.0100.

Disturbed flow regulates protein disulfide isomerase A1 expression via microRNA-204.

Tanaka L, Kumar S, Gutierre L, Magnun C, Kajihara D, Kang D Front Physiol. 2024; 15():1327794.

PMID: 38638277 PMC: 11024637. DOI: 10.3389/fphys.2024.1327794.

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists.

Siracusa C, Carino A, Carabetta N, Manica M, Sabatino J, Cianflone E J Clin Med. 2024; 13(5).

PMID: 38592207 PMC: 10932386. DOI: 10.3390/jcm13051405.

Expression of miRNA-29c in the carotid plaque and its association with diabetic mellitus.

Wang H, Mai P, He F, Zhang Y Front Cardiovasc Med. 2024; 11:1276066.

PMID: 38374991 PMC: 10875088. DOI: 10.3389/fcvm.2024.1276066.

References

Albinsson S, Nordstrom I, Hellstrand P . Stretch of the vascular wall induces smooth muscle differentiation by promoting actin polymerization. J Biol Chem. 2004; 279(33):34849-55. DOI: 10.1074/jbc.M403370200. View

Boettger T, Beetz N, Kostin S, Schneider J, Kruger M, Hein L . Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest. 2009; 119(9):2634-47. PMC: 2735940. DOI: 10.1172/JCI38864. View

Davis B, Hilyard A, Nguyen P, Lagna G, Hata A . Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype. J Biol Chem. 2008; 284(6):3728-38. PMC: 2635044. DOI: 10.1074/jbc.M808788200. View

Zhao Y, Ransom J, Li A, Vedantham V, von Drehle M, Muth A . Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell. 2007; 129(2):303-17. DOI: 10.1016/j.cell.2007.03.030. View

da Costa Martins P, Bourajjaj M, Gladka M, Kortland M, van Oort R, Pinto Y . Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation. 2008; 118(15):1567-76. DOI: 10.1161/CIRCULATIONAHA.108.769984. View

Long X, Tharp D, Georger M, Slivano O, Lee M, Wamhoff B . The smooth muscle cell-restricted KCNMB1 ion channel subunit is a direct transcriptional target of serum response factor and myocardin. J Biol Chem. 2009; 284(48):33671-82. PMC: 2785209. DOI: 10.1074/jbc.M109.050419. View

Xin M, Small E, Sutherland L, Qi X, McAnally J, Plato C . MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev. 2009; 23(18):2166-78. PMC: 2751981. DOI: 10.1101/gad.1842409. View

Xu N, Papagiannakopoulos T, Pan G, Thomson J, Kosik K . MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 2009; 137(4):647-58. DOI: 10.1016/j.cell.2009.02.038. View

Miano J . Serum response factor: toggling between disparate programs of gene expression. J Mol Cell Cardiol. 2003; 35(6):577-93. DOI: 10.1016/s0022-2828(03)00110-x. View

10.

Wirth A, Benyo Z, Lukasova M, Leutgeb B, Wettschureck N, Gorbey S . G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat Med. 2007; 14(1):64-8. DOI: 10.1038/nm1666. View

11.

Ishihara H, Ozaki H, Sato K, Hori M, Karaki H, Watabe S . Calcium-independent activation of contractile apparatus in smooth muscle by calyculin-A. J Pharmacol Exp Ther. 1989; 250(1):388-96. View

12.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

13.

Parmacek M . Myocardin-related transcription factors: critical coactivators regulating cardiovascular development and adaptation. Circ Res. 2007; 100(5):633-44. DOI: 10.1161/01.RES.0000259563.61091.e8. View

14.

Chen J, Mandel E, Thomson J, Wu Q, Callis T, Hammond S . The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2005; 38(2):228-33. PMC: 2538576. DOI: 10.1038/ng1725. View

15.

Bagi Z, Frangos J, Yeh J, White C, Kaley G, Koller A . PECAM-1 mediates NO-dependent dilation of arterioles to high temporal gradients of shear stress. Arterioscler Thromb Vasc Biol. 2005; 25(8):1590-5. DOI: 10.1161/01.ATV.0000170136.71970.5f. View

16.

Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H . MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res. 2007; 100(11):1579-88. DOI: 10.1161/CIRCRESAHA.106.141986. View

17.

Cheng Y, Liu X, Yang J, Lin Y, Xu D, Lu Q . MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res. 2009; 105(2):158-66. PMC: 2728297. DOI: 10.1161/CIRCRESAHA.109.197517. View

18.

Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C . A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 2009; 104(4):476-87. PMC: 2728290. DOI: 10.1161/CIRCRESAHA.108.185363. View

19.

Muljo S, Ansel K, Kanellopoulou C, Livingston D, Rao A, Rajewsky K . Aberrant T cell differentiation in the absence of Dicer. J Exp Med. 2005; 202(2):261-9. PMC: 2212998. DOI: 10.1084/jem.20050678. View

20.

Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico M . The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ. 2009; 16(12):1590-8. PMC: 3014107. DOI: 10.1038/cdd.2009.153. View