Title | Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Albinsson S, Skoura A, Yu J, DiLorenzo A, Fernández-Hernando C, Offermanns S, Miano JM, Sessa WC |
Journal | PLoS One |
Volume | 6 |
Issue | 4 |
Pagination | e18869 |
Date Published | 2011 Apr 22 |
ISSN | 1932-6203 |
Keywords | Animals, Animals, Newborn, Aorta, Biomarkers, Blood Pressure, Cell Differentiation, Gene Deletion, Gene Expression Regulation, Heart Function Tests, Mice, Mice, Knockout, MicroRNAs, Muscle Contraction, Muscle, Smooth, Vascular, Myocardium, Myocytes, Smooth Muscle, Organ Specificity, Ribonuclease III, Weight Loss |
Abstract | Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in postnatal vascular SMC has not been elucidated. Thus, the objective of this study was to identify the role of Dicer-dependent miRNAs for blood pressure regulation and vascular SMC contractile function and differentiation in vivo. Tamoxifen-inducible and SMC specific deletion of Dicer was achieved by Cre-Lox recombination. Deletion of Dicer resulted in a global loss of miRNAs in aortic SMC. Furthermore, Dicer-deficient mice exhibited a dramatic reduction in blood pressure due to significant loss of vascular contractile function and SMC contractile differentiation as well as vascular remodeling. Several of these results are consistent with our previous observations in SM-Dicer deficient embryos. Therefore, miRNAs are essential for maintaining blood pressure and contractile function in resistance vessels. Although the phenotype of miR-143/145 deficient mice resembles the loss of Dicer, the phenotypes of SM-Dicer KO mice were far more severe suggesting that additional miRNAs are involved in maintaining postnatal SMC differentiation. |
DOI | 10.1371/journal.pone.0018869 |
Alternate Journal | PLoS One |
PubMed ID | 21526127 |
PubMed Central ID | PMC3081311 |
Grant List | P01 HL070295 / HL / NHLBI NIH HHS / United States R01 HL61371 / HL / NHLBI NIH HHS / United States HL-62572 / HL / NHLBI NIH HHS / United States R01 HL64793 / HL / NHLBI NIH HHS / United States R01 HL064793 / HL / NHLBI NIH HHS / United States HL-091168 / HL / NHLBI NIH HHS / United States R01 HL096670 / HL / NHLBI NIH HHS / United States R01 HL091168 / HL / NHLBI NIH HHS / United States R01 HL062572 / HL / NHLBI NIH HHS / United States P01 HL70295 / HL / NHLBI NIH HHS / United States R01 HL081190 / HL / NHLBI NIH HHS / United States R01 HL061371 / HL / NHLBI NIH HHS / United States |
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