AI Article Synopsis
- The study investigates how aging affects endothelial cells, which are crucial for maintaining blood vessels and tissue health.
- RNA sequencing showed that in older mice, gene expression related to extracellular matrix proteins, particularly laminin β1 and β2, changes significantly, impacting the cells' functions.
- The findings suggest that a specific change in laminin expression due to aging can lead to problems with cell adhesion and movement, potentially contributing to organ dysfunction and fibrosis as we age.
Article Abstract
Objective: Endothelial cells play important roles in tissue homeostasis and vascularization, a function that is impaired by aging. Here, we aim to decipher the role of the microenvironment underlying the impairment of endothelial cell functions by aging.
Approach And Results: RNA sequencing of isolated cardiac endothelial cells derived from young and 18-month-old mouse hearts revealed that aging affects the endothelial expression of genes encoding extracellular matrix proteins, specifically the laminin β1 () and laminin β2 () chains. Whereas was upregulated, was decreased in endothelial cells in old mice compared with young controls. A similar change in expression patterns was observed after induction of acute myocardial infarction. Mimicking aging and injury conditions by plating endothelial cells on laminin β1-containing laminin 411 matrix impaired endothelial cell adhesion, migration, and tube formation and augmented endothelial-to-mesenchymal transition and endothelial detachment compared with laminin 421, which contains the laminin β2 chain. Because laminins can signal via integrin receptors, we determined the activation of ITGB1 (integrin β1). Laminin 421 coating induced a higher activation of ITGB1 compared with laminin 411. siRNA-mediated silencing of ITGB1 reduced laminin β2-dependent adhesion, suggesting that laminin β2 more efficiently activates ITGB1.
Conclusions: Mimicking age-related modulation of laminin β1 versus β2 chain expression changes the functional properties and phenotype of endothelial cells. The dysregulation of the extracellular matrix during vascular aging may contribute to age-associated impairment of organ function and fibrosis.
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| http://dx.doi.org/10.1161/ATVBAHA.117.310685 | DOI Listing |
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