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Notch1's absence increases the number of suicidal cells (green) in the stressed heart.
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The Notch pathway helps a developing heart get into shape. Croquelois et al. reveal on page 3173 that the pathway also helps a damaged heart reshape itself and keep pumping.
Weakened by a heart attack or the protracted stress of hypertension, the heart rebuilds itself as it struggles to maintain blood flow. To provide more pumping power, cardiomyocytes swell. Some studies suggest that heart stem cells begin proliferating to replace lost cardiomyocytes. Because the Notch pathway helps control self-renewal by other organs, Croquelois et al. thought it might also have a hand in heart remodeling.
When Notch1 was absent, they found, mice with stressed hearts showed signs of over-exuberant repair including thicker ventricular walls, increased fibrosis, and more of the telltale proteins fashioned by swollen cardiomyocytes. The mice and their heart muscle cells also had a higher-than-normal death rate. Loss of Notch also spurred more heart stem cells to differentiate. Notch might allow the heart to conserve these cells.
The Notch pathway triggers stem cell proliferation in skeletal muscle, and the pathway short-circuits as we age. The researchers say that it's possible the same deterioration occurs in the older heart, explaining why elderly people are more vulnerable to heart failure.
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