Statins shown to reduce Oxidized LDL stimulated redox signaling in endothelial cell membrane
A novel effect of statins directly inhibiting the membrane raft redox signaling in cultured endothelial cells highlights another possible benefit of statin therapy. The research has recently been published on line in The Journal of Pharmacology and Experimental Therapeutics.
Membranes of endothelial cells contain dynamic areas known as membrane rafts which are involved in mediating and amplifying cellular signals. Clusters of membrane rafts can form platforms for various signaling pathways. One such pathway (redox signaling) involves NADPH oxidase subunits and Rac GTPase that activate and enhance the production of superoxide. Superoxide is a toxic reactive oxygen species used by immune cells to combat infections. It is also associated with pathological disease states. Regulation of redox signaling is an important component of immunity and inflammation.
Investigators at Virginia Commonwealth University in Richmond, Virginia have published findings from their studies describing the effects of statins on this pathway. Coronary arterial endothelial cells treated in vitro with Medium Oxidized Low Density Lipoprotein (MOxLDL, Kalen Biomedical, LLC) form clusters of membrane rafts in the membranes. Pretreatment with statins (pravastatin or simvastatin) significantly inhibited the clustering. The statins directly reduced the aggregation of subunits of NADPH oxidase (gp91phox and p47phox). Additional mechanisms inhibited by statins include acid sphingomyelinase translocation and ceramide production. Electron spin resonance analysis of superoxide production in cultured cells shows an increase after treatment with MOxLDL. This increase was reduced when the cells were pretreated with statins.
The dysfunction of endothelium through chronic inflammation is a hallmark of cardiovascular disease. Statins have long been used as treatment to lower the chance of heart attacks and strokes because they lower cholesterol production in the liver. This work describes another mechanism that may be involved in the protective effect of statins in cardiovascular disease.
“Attenuation by Statins of Membrane Raft-Redox Signaling in Coronary Arterial Endothelium.”
The Journal of Pharmacology and Experimental Therapeutics
Published on February 22, 2013 as DOI:10.1124/jpet.112.201442
Yu-Miao Wei, Xiang Li, Jing Xiong, Justine M. Abais, Min Xia, Krishna M. Boini, Yang Zhang, Pin-Lan Li
Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia