Medical Research Council - London Institute of Medical Sciences

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Big Hearted

Role for kinase pathway identified in development of life-threatening heart enlargement

14 September 2022

Big Hearted

When faced with challenges like exercise, the heart can grow a little larger to supply more blood to needy organs, a process known as hypertrophy. Yet long-term enlargement, linked to stress caused by genetic conditions or high blood pressure, is dangerous, raising the risk of heart failure. Within cells, processes regulating hypertrophy involve enzymes in the p38 family, themselves activated by the protein kinases MKK6 and MKK3. In mice, researchers investigating the specific roles of these proteins uncovered complicated interactions between them, making it difficult to control hypertrophy. Removing MKK6 dampened the activity of one p38 protein, p38α, but other p38s were boosted in response, ultimately activating another pathway promoting hypertrophy: mice lacking MKK6 thus had much larger hearts (pictured, right) than typical mice (left), leading to further cardiac problems and shorter lifespans. Within this complex regulatory web, targeting other p38 components could provide more promising solutions in the future.

Written by Emmanuelle Briolat

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