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The intercalated disk is a cardiac specific structure composed of three main protein complexes—adherens junctions, desmosomes, and gap junctions—that work in concert to provide mechanical stability and electrical synchronization to the heart. Each substructure is regulated through a variety of mechanisms including proteolysis. Calpain proteases, a class of cysteine proteases dependent on calcium for activation, have recently emerged as important regulators of individual intercalated disk components. In this review, we will examine how calcium homeostasis regulates normal calpain function. We will also explore how calpains modulate gap junctions, desmosomes, and adherens junctions activity by targeting specific proteins, and describe the molecular mechanisms of how calpain dysregulation leads to structural and signaling defects within the heart. We will then examine how changes in calpain activity affects cardiomyocytes, and how such changes underlie various heart diseases.
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This content will become publicly available on March 1, 2026
Developmental and Evolutionary Heart Adaptations Through Structure–Function Relationships
While the heart works as an efficient pump, it also has a high level of adaptivity by changing its structure to maintain function during healthy and diseased states. In this Review, we present examples of structure–function relationships across species and throughout embryonic development in mammals and birds. We also summarize current research on avian models aiming at understanding how biophysical and biological mechanisms closely interact during heart formation. We conclude by underscoring similarities between cardiac adaptations and structural changes over developmental and evolutionary time scales and how understanding the mechanisms behind these adaptations can help prevent or alleviate the effects of cardiac malformations and contribute to cardiac regeneration efforts.
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- Award ID(s):
- 2109918
- PAR ID:
- 10626706
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Journal of Cardiovascular Development and Disease
- Volume:
- 12
- Issue:
- 3
- ISSN:
- 2308-3425
- Page Range / eLocation ID:
- 83
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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