HDL effect on TRPC channels and endothelial cell migration in arterial wound healing

Project: Research


  • Benjamin Abelson (PI)


Endothelial cell (EC) migration after angioplasty and stent placement is necessary for regeneration of a native endothelial cell layer, which is anti-thrombogenic and minimizes restenosis. Several factors have been found to inhibit EC migration, including lipid oxidation products, which may lead to increased rates of thrombosis and stenosis. Our laboratory has proposed the following mechanism through which lipid oxidation products, including lysophosphatidylcholine (lysoPC), inhibit EC migration: LysoPC activates canonical transient receptor potential channel 6 (TRPC6) which leads to an influx of calcium that activates TRPC5 channels. The subsequent rise in intracellular free calcium ion concentration activates calpain, which cleaves certain cytoskeletal proteins and inhibits migration. The mechanism by which the influx of calcium activates TRPC5 channels is not known, but we have found that: 1) Activation of NADPH oxidase (ROS) is a necessary component of this activation cascade; 2) NADPH oxidase inhibitors block the lysoPC-induced activation of TRPC5 but have no effect on lysoPC-induced TRPC6 activation; and, 3) HDL inhibits the lysoPC-induced production of ROS and blocks the TRPC6 activation cascade. We postulate that HDL blocks lysoPC-induced activation of NADPH oxidase and subsequent TRPC5 activation, and that HDL exerts its effect by stabilizing the EC membrane. Our results will suggest methods to limit restenosis or thrombosis after vascular intervention by limiting cellular dysfunction and promoting EC migration.
Award amount$25,000.00
Award date07/01/2012
Program typePredoctoral Fellowship
Award ID12PRE12060357
Effective start/end date07/01/201206/30/2013