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Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation
Open accessAbstract
As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood pressure without affecting SCN-controlled locomotor activity in murine models. In mesenteric arteries, BMAL1 bound to the promoter of and activated the transcription of Rho-kinase 2 (Rock2), and Bmal1 deletion abolished the time-of-day variations in response to agonist-induced vasoconstriction, myosin phosphorylation, and ROCK2 activation. Together, these data indicate that peripheral inputs contribute to the daily control of vasoconstriction and blood pressure and suggest that clock gene expression outside of the SCN should be further evaluated to elucidate pathogenic mechanisms of diseases involving blood pressure circadian rhythm disruption.
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“Functionally, targeted deletion of Bmal1 in murine vascular smooth muscle cells blunts the circadian amplitudes and advances the circadian phases of systolic and diastolic BP, and abolishes the circadian variation of pulse pressure (70).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [70]
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Metadata
- Authors
- Xie, Z., Su, W., Liu, S., Zhao, G., Esser, K., Schroder, E. A., Lefta, M., Stauss, H. M., Guo, Z., & Gong, M. C.
- Affiliations
- Anhui Agricultural University (CN)
- University of Kentucky (US)
- University of Iowa (US)
- Corresponding author
- Xie, Zhongwen
- Su, Wen
- Guo, Zhenheng
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2014-12-08
- Volume
- 125
- Issue
- 1
- Pages
- 324-336
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4382248
- OpenAlex
- W2135667255
- Cited by
- 189
- References
- 54
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 19 · 2023: 13 · 2022: 20 · 2021: 23 · 2020: 24 · 2019: 17 · 2018: 19 · 2017: 7 · 2016: 13 · 2015: 7
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion)
- Funders
- University of Kentucky (P20 GM103527, GM103527)
- National Institutes of Health (GM103527)
- National Heart, Lung, and Blood Institute (R01HL106843, HL088389, HL106843, R01HL088389)
- National Institute of General Medical Sciences (GM-103527, P20GM103527)
- National Institute of Environmental Health Sciences (RC1ES018636)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR066082)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- Bmal1, clock genes, circadian blood pressure rhythm, smooth muscle, ROCK2, vasoconstriction, myosin phosphorylation, mesenteric arteries, suprachiasmatic nucleus
- MeSH terms
- Animals, Blood Pressure, Circadian Rhythm, Enzyme Induction, Male, Mesenteric Arteries, Muscle Contraction, Muscle, Smooth, Vascular, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Vasoconstriction, Mice, Knockout, Myosin Light Chains, Muscle Development, rho-Associated Kinases, ARNTL Transcription Factors
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