Oxidized LDL signals through Rho-GTPase to induce endothelial cell stiffening and promote capillary formation

• DOI: 10.1194/jlr.m062539
• Publication Date: 2016-03-18T01:39:32Z
• Authors: Myung-Jin Oh; Chongxu Zhang; Elizabeth LeMaster; Crystal Adamos; Evgeny Berdyshev; Yedida Bogachkov; Erin E. Kohler; Jugajyoti Baruah; Yun Fang; Dean E. Schraufnagel; Kishore K. Wary; Irena Levitan
• Keywords: Myosin-light-chain phosphatase; Matrigel; Neointima; Oxysterol; CD31

Endothelial biomechanics is emerging as a key factor in endothelial function. Here, we address the mechanisms of stiffening induced by oxidized LDL (oxLDL) and investigate role oxLDL lumen formation. We show that oxLDL-induced mediated CD36-dependent activation RhoA its downstream target, Rho kinase (ROCK), via inhibition myosin light-chain phosphatase (MLCP) (MLC)2 phosphorylation. The LC-MS/MS analysis identifies 7-ketocholesterol (7KC) major oxysterol oxLDL. Similarly to oxLDL, 7KC induces activation, MLCP inhibition, MLC2 phosphorylation resulting stiffening. OxLDL also facilitates formation branching networks 3D collagen gels vitro increased functional blood vessels Matrigel plug assay vivo. Both effects are ROCK dependent. An increase was observed response pre-exposing cells 7KC, an stiffening, but not 5α,6α epoxide does affect stiffness. Importantly, loading with cholesterol prevented signaling cascade, reversed In summary, CD36/RhoA/ROCK/MLCP/MLC2 pathway associated angiogenic activity.