Dataset Information

Remodeling of the cardiac extracellular matrix proteome during chronological and pathological aging

ABSTRACT: 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. Here, we 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 proteins quantified, we identified 13 proteins that were increased, including lactadherin (MFGE8), collagen VI 6 (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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Emilio Cirri

LAB HEAD: Alessandro Ori

PROVIDER: PXD039548 | Pride | 2024-01-08

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	180330_IH_DS_FFPE_Human_Heart_TMT10_24frHpH_fr1.msf	Msf
	180330_IH_DS_FFPE_Human_Heart_TMT10_24frHpH_fr1.raw	Raw
	180330_IH_DS_FFPE_Human_Heart_TMT10_24frHpH_fr10.raw	Raw
	180330_IH_DS_FFPE_Human_Heart_TMT10_24frHpH_fr11.raw	Raw
	180330_IH_DS_FFPE_Human_Heart_TMT10_24frHpH_fr12.raw	Raw

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Publications

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

Santinha Deolinda D Vilaça Andreia A Estronca Luís L Schüler Svenja C SC Bartoli Catherine C De Sandre-Giovannoli Annachiara A Figueiredo Arnaldo A Quaas Maximillian M Pompe Tilo T Ori Alessandro A Ferreira Lino L

Molecular & cellular proteomics : MCP 20231221 1

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 ...[more]

PMID: 38141925

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