Mass spectrometry of murine atria revealed 237 differentially expressed ECM proteins with age, showing a marked decrease in overall collagen content rather than an increase.
Age-associated atrial stiffness in mice may be driven by increased collagen cross-linking rather than increased collagen content, highlighting novel protein targets for cardiac aging.
The cardiac atrial extracellular matrix (ECM) is central to age-associated cardiac remodeling and subsequent decline in cardiac functioning. Despite this, the composition of the atrial ECM and how it changes with age is not yet known. This study utilized mass spectrometry to evaluate the composition of murine atria in young (12 weeks) and old (77 weeks) C57BL/6J mice. The tissue was decellularized, ECM and ECM-associated proteins were extracted with GuHCl, and proteins were deglycosylated to enable identification of glycosylated peptides. Two hundred and thirty-seven ECM and ECM-associated proteins were found to be significantly differentially expressed with age. Some proteins (MMP9, S100A9, VWA3A, CTSD, CCL8) were more than threefold increased with age, proteoglycans were modestly decreased, while the overall collagen content was markedly decreased. STRING network mapping of physical associations predicted that both PLOD3 and PDGFA interact with the collagens that decreased with age. The results suggest that the mechanism behind age-associated atrial stiffness is not due to an increase in collagen content as previously believed, but an increase in cross-linking, potentially facilitated by PLOD3. Additionally, several of the significant proteins have not previously been associated with cardiac aging and thus are potential drug targets for age-associated cardiac fibrosis and other age-associated conditions.
Ringström et al. (Mon,) conducted a other in Age-associated cardiac remodeling. Aging (77 weeks) vs. Young mice (12 weeks) was evaluated on Composition of the atrial extracellular matrix (ECM). Mass spectrometry of murine atria revealed 237 differentially expressed ECM proteins with age, showing a marked decrease in overall collagen content rather than an increase.