Dynamics of collagen oxidation and cross linking in regenerating and irreversibly infarcted myocardium

Eman A. Akam-Baxter (), David Bergemann, Sterling J. Ridley, Samantha To, Brittany Andrea, Brianna Moon, Hua Ma, Yirong Zhou, Aaron Aguirre, Peter Caravan, Juan Manuel Gonzalez-Rosa and David E. Sosnovik
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Eman A. Akam-Baxter: Harvard Medical School
David Bergemann: Harvard Medical School
Sterling J. Ridley: Harvard Medical School
Samantha To: Harvard Medical School
Brittany Andrea: Harvard Medical School
Brianna Moon: Harvard Medical School
Hua Ma: Harvard Medical School
Yirong Zhou: Harvard Medical School
Aaron Aguirre: Harvard Medical School
Peter Caravan: Massachusetts General Hospital
Juan Manuel Gonzalez-Rosa: Harvard Medical School
David E. Sosnovik: Harvard Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract In mammalian hearts myocardial infarction produces a permanent collagen-rich scar. Conversely, in zebrafish a collagen-rich scar forms but is completely resorbed as the myocardium regenerates. The formation of cross-links in collagen hinders its degradation but cross-linking has not been well characterized in zebrafish hearts. Here, a library of fluorescent probes to quantify collagen oxidation, the first step in collagen cross-link (CCL) formation, was developed. Myocardial injury in mice or zebrafish resulted in similar dynamics of collagen oxidation in the myocardium in the first month after injury. However, during this time, mature CCLs such as pyridinoline and deoxypyridinoline developed in the murine infarcts but not in the zebrafish hearts. High levels of newly oxidized collagen were still seen in murine scars with mature CCLs. These data suggest that fibrogenesis remains dynamic, even in mature scars, and that the absence of mature CCLs in zebrafish hearts may facilitate their ability to regenerate.

Date: 2024
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DOI: 10.1038/s41467-024-48604-7

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