Journal article
MiR-204 regulates type 1 IP3R to control vascular smooth muscle cell contractility and blood pressure
Cell calcium (Edinburgh), Vol.80, pp.18-24
06/2019
DOI: 10.1016/j.ceca.2019.03.006
PMCID: PMC6767906
PMID: 30925290
Abstract
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•miR-204 selectively target IP3R1in vascular smooth muscle cells.•miR-204 regulates calcium release from the endoplasmic reticulum.•miR-204 controls vascular smooth muscle cells contractility.•miR-204 plays an important role in regulating blood pressure.
MiR-204 is expressed in vascular smooth muscle cells (VSMC). However, its role in VSMC contraction is not known. We determined if miR-204 controls VSMC contractility and blood pressure through regulation of sarcoplasmic reticulum (SR) calcium (Ca2+) release. Systolic blood pressure (SBP) and vasoreactivity to VSMC contractile agonists (phenylephrine (PE), thromboxane analogue (U46619), endothelin-1 (ET-1), angiotensin-II (Ang II) and norepinephrine (NE) were compared in aortas and mesenteric resistance arteries (MRA) from miR-204−/− mice and wildtype mice (WT). There was no difference in basal systolic blood pressure (SBP) between the two genotypes; however, hypertensive response to Ang II was significantly greater in miR-204−/− mice compared to WT mice. Aortas and MRA of miR-204−/− mice had heightened contractility to all VSMC agonists. In silico algorithms predicted the type 1 Inositol 1, 4, 5-trisphosphate receptor (IP3R1) as a target of miR-204. Aortas and MRA of miR-204−/− mice had higher expression of IP3R1 compared to WT mice. Difference in agonist-induced vasoconstriction between miR-204−/− and WT mice was abolished with pharmacologic inhibition of IP3R1. Furthermore, Ang II-induced aortic IP3R1 was greater in miR-204−/− mice compared to WT mice. In addition, difference in aortic vasoconstriction to VSMC agonists between miR-204−/− and WT mice persisted after Ang II infusion. Inhibition of miR-204 in VSMC in vitro increased IP3R1, and boosted SR Ca2+ release in response to PE, while overexpression of miR-204 downregulated IP3R1. Finally, a sequence-specific nucleotide blocker that targets the miR-204-IP3R1 interaction rescued miR-204-induced downregulation of IP3R1. We conclude that miR-204 controls VSMC contractility and blood pressure through IP3R1-dependent regulation of SR calcium release.
Details
- Title: Subtitle
- MiR-204 regulates type 1 IP3R to control vascular smooth muscle cell contractility and blood pressure
- Creators
- Mohanad Gabani - Roy J. and Lucille A. Carver College of MedicineJing Liu - Roy J. and Lucille A. Carver College of MedicineKarima Ait-Aissa - University of IowaOlha Koval - University of IowaYoung-Rae Kim - University of IowaDiana Castañeda - California State University Los AngelesAjit Vikram - University of IowaJulia S. Jacobs - Roy J. and Lucille A. Carver College of MedicineIsabella Grumbach - University of IowaMohamed Trebak - Pennsylvania State UniversityKaikobad Irani - Roy J. and Lucille A. Carver College of MedicineModar Kassan - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Cell calcium (Edinburgh), Vol.80, pp.18-24
- DOI
- 10.1016/j.ceca.2019.03.006
- PMID
- 30925290
- PMCID
- PMC6767906
- NLM abbreviation
- Cell Calcium
- ISSN
- 0143-4160
- eISSN
- 1532-1991
- Publisher
- Elsevier Ltd
- Grant note
- name: VA Merit, award: I01 BX002940-04; name: University of Iowa Endowed Professorship in Cardiovascular Medicine; name: NIH, award: T32 HL007121, AHA-18CDA34030155
- Language
- English
- Date published
- 06/2019
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984313860102771
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