Remodelling of the cardiac extracellular matrix proteome during chronological and pathological ageing

Mol Cell Proteomics. 2023 Dec 21:100706. doi: 10.1016/j.mcpro.2023.100706. Online ahead of print.ABSTRACTImpaired extracellular matrix (ECM) remodelling is a hallmark of many chronic inflammatory disorders that can lead to cellular dysfunction, ageing, and disease progression. The ECM of the aged heart and its effects on cardiac cells during chronological and pathological ageing are poorly understood across species. For this purpose, we first used mass spectrometry-based proteomics to quantitatively characterize age-related remodelling of the left ventricle (LV) of mice and humans during chronological and pathological (Hutchinson-Gilford progeria syndrome (HGPS)) ageing. 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 analysed. 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 ageing phenotype. These results extend our knowledge of the LV proteome remodelling induced by chronological and pathological ag...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research