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Mechanisms of oxLDL on Endothelial Biomechanics
Author(s) -
Oh Myung-Jin,
Shentu Tzu-Pin,
Levitan Irena
Publication year - 2012
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.26.1_supplement.840.6
Subject(s) - rhoa , rho associated protein kinase , microbiology and biotechnology , stress fiber , cytoskeleton , actin cytoskeleton , endothelial stem cell , chemistry , actin , myosin light chain kinase , myosin , effector , cell , signal transduction , biology , in vitro , biochemistry
Oxidized low density lipoprotein (oxLDL) is a major factor in the initiation and development of atherosclerosis. Our lab has shown that oxLDL increases endothelial stiffness suggesting that changes in endothelial biomechanics are important for endothelial dysfunction. The mechanisms, however, by which oxLDL alters endothelial biomechanics are not understood. Our goal is to elucidate the mechanisms of oxLDL‐induced cell stiffening. Since cell stiffness is determined by the cytoskeleton, in particular the actin cytoskeleton, we tested whether oxLDL‐induced cell stiffening is mediated by the Rho‐GTPases, the major regulators of actin cytoskeleton dynamics. We targeted RhoA, that induces stress fiber formation. We show that oxLDL induced cell stiffness is abrogated by inhibiting RhoA with C3 transferase, suggesting that RhoA and its downstream targets are involved in oxLDL induced cell stiffening. We next explored the role of Rho kinase (ROCK), an immediate downstream effector of RhoA. Inhibition of ROCK by Y27632 also inhibited oxLDL induced cell stiffening. In contrast, inhibiting myosin light chain kinase (MLCK) by ML7 had no effect on oxLDL induced cell stiffness. We propose, therefore, that oxLDL‐induced endothelial stiffening is mediated by the RhoA/ROCK pathway and plays an important role in dyslipidemic conditions in vivo. (Supported by HL083298)