| First Author | Wagner JUG | Year | 2018 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
| Issue | 5 | Pages | 1170-1177 |
| PubMed ID | 29599141 | Mgi Jnum | J:285155 |
| Mgi Id | MGI:6385468 | Doi | 10.1161/ATVBAHA.117.310685 |
| Citation | Wagner JUG, et al. (2018) Switch in Laminin beta2 to Laminin beta1 Isoforms During Aging Controls Endothelial Cell Functions-Brief Report. Arterioscler Thromb Vasc Biol 38(5):1170-1177 |
| abstractText | 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 beta1 (Lamb1) and laminin beta2 (Lamb2) chains. Whereas Lamb1 was upregulated, Lamb2 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 beta1-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 beta2 chain. Because laminins can signal via integrin receptors, we determined the activation of ITGB1 (integrin beta1). Laminin 421 coating induced a higher activation of ITGB1 compared with laminin 411. siRNA-mediated silencing of ITGB1 reduced laminin beta2-dependent adhesion, suggesting that laminin beta2 more efficiently activates ITGB1. CONCLUSIONS: Mimicking age-related modulation of laminin beta1 versus beta2 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. |
