Blood | VOL. 118
Read

12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation

Publication Date Nov 17, 2011

Abstract

Abstract To understand the mechanisms by which 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) activates Rac1 in the induction of angiogenesis, we studied the role of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase and αPix. 15(S)-HETE stimulated Rac1 in a sustained manner in human dermal microvascular endothelial cells (HDMVECs). Simvastatin, a potent inhibitor of HMG-CoA reductase, suppressed 15(S)-HETE–induced Rac1 activation in HDMVECs affecting their migration and tube formation. 15(S)-HETE by inducing HMG-CoA reductase expression caused increased farnesylation and membrane translocation of Rac1 where it became activated by Src-dependent αPix stimulation. Mevalonate rescued 15(S)-HETE–induced Rac1 farnesylation and membrane translocation in HDMVECs and the migration and tube formation of these cells from inhibition by simvastatin. Down-regulation of αPix inhibited 15(S)-HETE–induced HDMVEC migration and tube formation. Hind-limb ischemia induced Rac1 farnesylation and activation leading to increased angiogenesis and these effects were blocked by simvastatin and rescued by mevalonate in WT mice. In contrast, hind-limb ischemia failed to induce Rac1 farnesylation and activation as well as angiogenic response in 12/15-Lox−/− mice. Activation of Src and αPix were also compromised at least to some extent in 12/15-Lox−/− mice compared with WT mice in response to hind-limb ischemia. Together, these findings demonstrate for the first time that HMG-CoA reductase plays a determinant role in 12/15-Lox–indu...

Concepts

Human Dermal Microvascular Endothelial Cells Potent Inhibitor Of HMG-CoA Reductase Membrane Translocation Of Rac1 Hind-limb Ischemia HMG-CoA Reductase Rac1 Activation WT Mice Tube Formation Induction Of Angiogenesis Activation Of Src

Round-ups are the summaries of handpicked papers around trending topics published every week. These would enable you to scan through a collection of papers and decide if the paper is relevant to you before actually investing time into reading it.

Climate change Research Articles published between Nov 14, 2022 to Nov 20, 2022

R DiscoveryNov 21, 2022
R DiscoveryArticles Included:  2

The world needs to move quickly towards sustainability that should characterize all production and consumption patterns. We use cookies to improve you...

Read More

Coronavirus Pandemic

You can also read COVID related content on R COVID-19

R ProductsCOVID-19

ONE PROBLEM . ONE PURPOSE . ONE PLACE

Creating the world’s largest AI-driven & human-curated collection of research, news, expert recommendations and educational resources on COVID-19

COVID-19 Dashboard

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on “as is” basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The Copyright Law.