ArticleJournal of molecular and cellular cardiology2014
Calcineurin and its regulator, RCAN1, confer time-of-day changes in susceptibility of the heart to ischemia/reperfusion.
Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Restoring RCAN1 dosage mitigates sleep and EEG abnormalities in a Down syndrome model.Neurobiology of disease · 2026Article
- Review
- Circadian Effects on Vascular Immunopathologies.Circulation research · 2024Review
- The Cardiac Circadian Clock: Implications for Cardiovascular Disease and its Treatment.JACC. Basic to translational science · 2023Review
- Circadian regulation of cardiac muscle function and protein degradation.Chronobiology international · 2023Article
- RCAN1 deficiency aggravates sepsis-induced cardiac remodeling and dysfunction by accelerating mitochondrial pathological fission.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Regulator of calcineurin 1 deletion attenuates mitochondrial dysfunction and apoptosis in acute kidney injury through JNK/Mff signaling pathway.Cell death & disease · 2022Article
- Article
- Article
- RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging.Journal of neurodevelopmental disorders · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- Methamphetamine-induced changes in myocardial gene transcription are sex-dependent.BMC genomics · 2021Article
- Mechanism of circadian regulation of the NRF2/ARE pathway in renal ischemia-reperfusion.Experimental and therapeutic medicine · 2021Article
- Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro.International journal of molecular sciences · 2021Article
- PER2 Regulates Reactive Oxygen Species Production in the Circadian Susceptibility to Ischemia/Reperfusion Injury in the Heart.Oxidative medicine and cellular longevity · 2021Article
- Reciprocal Relationship Between Calcium Signaling and Circadian Clocks: Implications for Calcium Homeostasis, Clock Function, and Therapeutics.Frontiers in molecular neuroscience · 2021Review
- RCAN1 in cardiovascular diseases: molecular mechanisms and a potential therapeutic target.Molecular medicine (Cambridge, Mass.) · 2020Review
- Combination effects of a fatty diet and exercise on the depressive state and cardioprotection in apolipoprotein E knockout mice with a change inThe Journal of international medical research · 2020Article
- Regulator of Calcineurin (RCAN): Beyond Down Syndrome Critical Region.Molecules and cells · 2020Review
- Chronobiological Influence Over Cardiovascular Function: The Good, the Bad, and the Ugly.Circulation research · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Many important components of the cardiovascular system display circadian rhythmicity. In both humans and mice, cardiac damage from ischemia/reperfusion (I/R) is greatest at the transition from sleep to activity. The causes of this window of susceptibility are not fully understood. In the murine heart we have reported high amplitude circadian oscillations in the expression of the cardioprotective protein regulator of calcineurin 1 (Rcan1). This study was designed to test whether Rcan1 contributes to the circadian rhythm in cardiac protection from I/R damage. Wild type (WT), Rcan1 KO, and Rcan1-Tg mice, with cardiomyocyte-specific overexpression of Rcan1, were subjected to 45min of myocardial ischemia followed by 24h of reperfusion. Surgeries were performed either during the first 2h (AM) or during the last 2h (PM) of the animal's light phase. The area at risk was the same for all genotypes at either time point; however, in WT mice, PM-generated infarcts were 78% larger than AM-generated infarcts. Plasma cardiac troponin I levels were likewise greater in PM-operated animals. In Rcan1 KO mice there was no significant difference between the AM- and PM-operated hearts, which displayed greater indices of damage similar to that of PM-operated WT animals. Mice with cardiomyocyte-specific overexpression of human RCAN1, likewise, showed no time-of-day difference, but had smaller infarcts comparable to those of AM-operated WT mice. In vitro, cardiomyocytes depleted of RCAN1 were more sensitive to simulated I/R and the calcineurin inhibitor, FK506, restored protection. FK506 also conferred protection to PM-infarcted WT animals. Importantly, transcription of core circadian clock genes was not altered in Rcan1 KO hearts. These studies identify the calcineurin/Rcan1-signaling cascade as a potential therapeutic target through which to benefit from innate circadian changes in cardiac protection without disrupting core circadian oscillations that are essential to cardiovascular, metabolic, and mental health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.