Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis
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Chronic kidney disease in mice leads to disturbances in the biological time-keeping machinery of white blood cells, spurring inflammation that can damage the heart.
Just under one in ten people are thought to suffer from chronic kidney disease globally. People with kidney disease often have heart problems, but the connections between the two disorders have not been fully teased out.
Now, 12 Kyushu University researchers and a collaborator have surgically induced kidney disease in mice, which caused vitamin A levels to build up in the bloodstream. The jolt of vitamin A disrupted the circadian rhythms of monocytes, a type of white blood cell, leading to enhanced expression of a pro-inflammatory protein and the infiltration of these cells into the heart, with detrimental effects.
In mice with genetic defects in their circadian clocks, the pro-inflammatory signalling cascade broke down and the heart was spared from attack.
These findings could help to identify new therapeutic targets for treating the cardiovascular complications of kidney disease.
- Nature Communications 12, 2783 (2021). doi: 10.1038/s41467-021-23050-x
|Kyushu University, Japan||0.92|
|Saiseikai Nagasaki Hospital, Japan||0.08|