Knockdown of angiopoietin-like 2 induces clearance of vascular endothelial senescent cells by apoptosis, promotes endothelial repair and slows atherogenesis in mice.

ABSTRACT: Elimination of senescent cells (SnC) is anti-atherogenic, but the specific contribution of senescent vascular endothelial cells (EC) is unknown. We inactivated angiopoietin like-2 (angptl2), a marker of SnEC and a pro-atherogenic cytokine in LDLr^-/-, hApoB₁₀₀^+/+ atherosclerotic (ATX) mice. Three months after a single vascular delivery of a small hairpin (sh)Angptl2 in 3-month old ATX mice using an adeno-associated virus serotype 1 (AAV1), aortic atheroma plaque progression was slowed by 58% (p<0.0001). In the native aortic endothelium, angptl2 expression was decreased by 80%, in association with a reduced expression of p21, a cyclin-dependent kinase inhibitor overexpressed in growth-arrested SnC. Endothelial activation was reduced (lower Ic

SUBMITTER: Caland L 

PROVIDER: S-EPMC6594793 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature