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Mechanisms of oxLDL induced endothelial stiffening and its role in capillary formation
Author(s) -
Oh MyungJin,
Shentu TzuPin,
Kohler Erin,
Wary Kishore,
Levitan Irena
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.916.10
Subject(s) - rhoa , stiffening , chemistry , microbiology and biotechnology , matrigel , endothelial stem cell , dyslipidemia , endothelial dysfunction , in vivo , endothelium , medicine , signal transduction , biology , in vitro , materials science , biochemistry , composite material , obesity
Dyslipidemia is a major risk factor for the development of atherosclerosis which is initiated by endothelial injury but the mechanisms of dyslipidemia‐induced endothelial injury are still poorly understood. Our lab has shown that plasma dyslipidemia, oxidized low density lipoprotein (oxLDL), and 7‐ketocholesterol, leads to an increase in endothelial cell (EC) stiffness. We propose that endothelial stiffening plays a significant role in neovascularization of atherosclerotic plaques. Our goal is to understand the mechanism by which oxLDL induces EC stiffening and whether EC stiffening contributes to the formation of capillaries. We tested whether oxLDL‐induced EC stiffening is mediated by the Rho‐GTPases. We specifically targeted RhoA or its downstream effector Rho kinase (ROCK). We show that oxLDL induced EC stiffening is abrogated when inhibiting either RhoA or ROCK, and 7‐ketocholesterol induced EC stiffening is also abrogated by inhibition of RhoA. To test whether oxLDL is involved in capillary formation in vivo, we performed a matrigel plug assay and quantified the number of vessels formed from cells exposed to oxLDL. We show that oxLDL induces an increase in the number of vessels formed compared to normal vessel formation. We propose, therefore, that oxLDL induced endothelial stiffening is mediated by the RhoA/ROCK pathway, and that it plays an important role in dyslipidemic conditions in vivo.