Remodeling of the Cardiac Extracellular Matrix Proteome During Chronological and Pathological Aging

Impaired extracellular matrix (ECM) remodeling is a hallmark of many chronic inflammatory disorders that can lead to cellular dysfunction, aging, and disease progression. The ECM of the aged heart and its effects on cardiac cells during chronological and pathological aging are poorly understood acro...

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Published in:Molecular & cellular proteomics 2024-01, Vol.23 (1), p.100706-100706, Article 100706
Main Authors: Santinha, Deolinda, Vilaça, Andreia, Estronca, Luís, Schüler, Svenja C., Bartoli, Catherine, De Sandre-Giovannoli, Annachiara, Figueiredo, Arnaldo, Quaas, Maximillian, Pompe, Tilo, Ori, Alessandro, Ferreira, Lino
Format: Article
Language:English
Subjects:
aging
Aging - metabolism
cardiac aging
decellularization
Endothelial Cells - metabolism
extracellular matrix
Extracellular Matrix - metabolism
Extracellular Matrix Proteins - metabolism
Heart
Humans
Hutchinson-Gilford progeria syndrome
lactadherin
matrisome
Proteome - metabolism
proteomic
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Summary:Impaired extracellular matrix (ECM) remodeling is a hallmark of many chronic inflammatory disorders that can lead to cellular dysfunction, aging, and disease progression. The ECM of the aged heart and its effects on cardiac cells during chronological and pathological aging are poorly understood across species. For this purpose, we first used mass spectrometry-based proteomics to quantitatively characterize age-related remodeling of the left ventricle (LV) of mice and humans during chronological and pathological (Hutchinson-Gilford progeria syndrome (HGPS)) aging. Of the approximately 300 ECM and ECM-associated proteins quantified (named as Matrisome), we identified 13 proteins that were increased during aging, including lactadherin (MFGE8), collagen VI α6 (COL6A6), vitronectin (VTN) and immunoglobulin heavy constant mu (IGHM), whereas fibulin-5 (FBLN5) was decreased in most of the data sets analyzed. We show that lactadherin accumulates with age in large cardiac blood vessels and when immobilized, triggers phosphorylation of several phosphosites of GSK3B, MAPK isoforms 1, 3, and 14, and MTOR kinases in aortic endothelial cells (ECs). In addition, immobilized lactadherin increased the expression of pro-inflammatory markers associated with an aging phenotype. These results extend our knowledge of the LV proteome remodeling induced by chronological and pathological aging in different species (mouse and human). The lactadherin-triggered changes in the proteome and phosphoproteome of ECs suggest a straight link between ECM component remodeling and the aging process of ECs, which may provide an additional layer to prevent cardiac aging. [Display omitted] •Chronological and pathological aging alters the matrisome of mouse and human myocardium.•Decellularization enables deeper characterization of age-related alterations in the matrisome.•Lactadherin is a cardiovascular aging marker that accumulates in large vessels.•Lactadherin increases the phosphorylation of signaling pathways linked with aging. Our study, using recent proteomic methods and strategies to characterize cardiac samples (e.g. decellularization), provides new insights into how the cardiac tissue ages, particularly the left ventricle, during chronological and pathological (accelerated) aging. Our results show that the extracellular matrix, secreted by cells, is significantly altered during aging. We further show that lactadherin is a cardiovascular aging marker that accumulates in the vasculature of t
ISSN:1535-9476
1535-9484
DOI:10.1016/j.mcpro.2023.100706