Statin-specific inhibition of Rab-GTPase regulates cPKC-mediated IKs internalization

Elsa Ronzier, Xiaorong Xu Parks, Haani Qudsi, Coeli M. Lopes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Statins are prescribed for prevention and treatment of coronary artery disease. Statins have different cholesterol lowering abilities, with rosuvastatin and atorvastatin being the most effective, while statins like simvastatin and fluvastatin having lower effectiveness. Statins, in addition to their cholesterol lowering effects, can prevent isoprenylation of Rab-GTPase proteins, a protein family important for the regulation of membrane-bound protein trafficking. Here we show that endosomal localization of Rab-GTPases (Rab5, Rab7 and Rab11) was inhibited in a statin-specific manner, with stronger effects by fluvastatin, followed by simvastatin and atorvastatin, and with a limited effect by rosuvastatin. Fluvastatin inhibition of Rab5 has been shown to mediate cPKC-dependent trafficking regulation of the cardiac delayed rectifier KCNQ1/KCNE1 channels. We observed statin-specific inhibition of channel regulation consistent with statin-specific Rab-GTPase inhibition both in heterologous systems and cardiomyocytes. Our results uncover a non-cholesterol-reducing statin-specific effect of statins. Because Rab-GTPases are important regulators of membrane trafficking they may underlie statin specific pleiotropic effects. Therefore, statin-specificity may allow better treatment tailoring.

Original languageEnglish
Article number17747
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2019
Externally publishedYes


Dive into the research topics of 'Statin-specific inhibition of Rab-GTPase regulates cPKC-mediated IKs internalization'. Together they form a unique fingerprint.

Cite this