All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
Study explains why asthma, heart attacks and other conditions often occur in the early morning hours
Last reviewed: 02.07.2025
Researchers in the lab of Professor Gad Asher at the Weizmann Institute of Science have made a major discovery: a key component of circadian rhythms, a protein called BMAL1, regulates the body’s response to oxygen deprivation. The findings, published in Cell Metabolism, help explain why many oxygen-deficient conditions are time-dependent.
The role of circadian rhythms and oxygen deficiency
Circadian rhythms are a 24-hour internal molecular mechanism that regulates processes in every cell of the body. The protein BMAL1, known as the cell's "clock," interacts with another key protein, HIF-1α, which is activated when oxygen is lacking.
- HIF-1α: With normal oxygen levels, this protein is quickly destroyed. However, with its deficiency, HIF-1α stabilizes, accumulates and activates genes that help adapt to hypoxia.
- BMAL1: Research has shown that this circadian protein not only enhances HIF-1α function, but also plays an independent role in the body's response to oxygen deficiency.
Experiment with mice
To study the relationship between circadian rhythms and the response to hypoxia, the researchers created three groups of genetically modified mice:
- HIF-1α was not produced in liver tissue.
- Did not produce BMAL1.
- Both proteins were not produced.
Results:
- When oxygen levels dropped, the absence of BMAL1 prevented the accumulation of HIF-1α, which impaired the genetic response to hypoxia.
- Mice lacking both proteins had low survival rates depending on the time of day, with mortality being particularly high at night.
Conclusions: BMAL1 and HIF-1α play a key role in protecting the body from hypoxia, and circadian rhythms are directly related to the body's response to oxygen deficiency.
Liver pathology and the connection with the lungs
In mice without both proteins in their livers, the researchers found low blood oxygen levels even before exposure to hypoxia, raising suspicions that the deaths were related to impaired lung function.
- These mice developed hepatopulmonary syndrome, a condition in which blood vessels in the lungs dilate, increasing blood flow but reducing the efficiency of oxygen uptake.
- The analysis showed increased production of nitric oxide in the lungs, which increased vasodilation (widening of blood vessels).
Significance of the study
- Chronobiology of disease: The findings explain why patients with hypoxia or diseases such as asthma or heart attacks become worse at certain times of the day.
- Disease models: Mice lacking HIF-1α and BMAL1 have become the first genetic model to study hepatopulmonary syndrome, opening up new avenues for treatment.
- Treatment prospects: The study suggests that targeted drugs that regulate proteins involved in liver-lung communication could be a new treatment option.
"We are just beginning to understand the complex mechanisms linking circadian rhythms, hypoxia and inter-organ interactions," said Professor Asher. "These discoveries may lead to new treatments for diseases associated with oxygen deficiency."