Cited by 189Circadian rhythm and melatoninBlood Pressure and Hypertension StudiesRenin-Angiotensin System Studies

Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation

Open access
Xie, Zhongwen, Su, Wen, Liu, Shu, Zhao, Guogang, Esser, Karyn, Schroder, Elizabeth A., Lefta, Mellani, Stauss, Harald M. +2 more·2015·Journal of Clinical Investigation

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1172/jci76881

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Targeted deletion of Bmal1 in murine vascular smooth muscle cells blunts the circadian amplitudes and advances the circadian phases of systolic and diastolic blood pressure, and abolishes the circadian variation of pulse pressure.

    “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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Su W, Xie Z, Guo Z, Duncan MJ, Lutshumba J, Gong MC. Altered clock gene expression and vascular smooth muscle diurnal contractile vari- ations in type 2 diabetic db/db mice. Am J Physiol Heart Circ Physiol. 2012;302(3):H621-H633.
  2. Golombek DA, Rosenstein RE. Physiol- ogy of circadian entrainment. Physiol Rev. 2010;90(3):1063-1102.
  3. Schroder EA, et al. The cardiomyocyte molecu- lar clock, regulation of Scn5a, and arrhyth- mia susceptibility. Am J Physiol Cell Physiol. 2013;304(10):C954-C965.
  4. Xie Z, Gong MC, Su W, Xie D, Turk J, Guo Z. Role of calcium-independent phospholipase A2beta in high glucose-induced activation of RhoA, Rho kinase, and CPI-17 in cultured vascular smooth muscle cells and vascular smooth muscle hyper- contractility in diabetic animals. J Biol Chem. 2010;285(12):8628-8638.

Cited by

Sorted by citations

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
Venue
Journal of Clinical Investigation
Published
2014-12-08
Volume
125
Issue
1
Pages
324-336
ISSN
0021-9738 (ISSN-L)
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review