Novel actions of HMG-CoA reductase inhibitors(statins)--vascular and cerebral protection through inhibition of small GTPase Rho

N. Sawada, Hiroshi Itoh, K. Nakao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Clinical trials have demonstrated the beneficial effect of HMG-CoA reductase inhibitors(statins) for stroke prevention, independent of their lipid-lowering effects. Recent experimental progress indicated the effects of statins for brain protection on both vascular walls(endothelium, smooth muscle, inflammatory cells and platelets) and extra-vascular tissues(brain parenchyma). These pleiotropic effects of statins have been, at least in part, ascribed to inhibition of small GTPases Rho and Ras, which require isoprenoids (intermediates of the cholesterol biosynthesis pathway) for activation. Importantly, statin inhibition of Rho (1) attenuates the infarct size in a rat model of brain ischemia via the elevation of eNOS expression, and (2) suppresses vascular smooth muscle proliferation through up-regulation of CDK inhibitor p27kip1. The novel action of statin, as inhibitor of small GTPase family, should expand its potential toward integrative organ protection, beyond its conventional lipid-lowering and anti-atherogenic effects.

Original languageEnglish
Pages (from-to)2470-2475
Number of pages6
JournalNippon rinsho. Japanese journal of clinical medicine
Volume59
Issue number12
Publication statusPublished - 2001 Dec
Externally publishedYes

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Monomeric GTP-Binding Proteins
Blood Vessels
Lipids
Terpenes
Vascular Endothelium
Brain
Brain Ischemia
Vascular Smooth Muscle
Smooth Muscle Myocytes
Up-Regulation
Blood Platelets
Stroke
Cholesterol
Clinical Trials

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{b78e1d6bfd494782a45b28802dde0493,
title = "Novel actions of HMG-CoA reductase inhibitors(statins)--vascular and cerebral protection through inhibition of small GTPase Rho",
abstract = "Clinical trials have demonstrated the beneficial effect of HMG-CoA reductase inhibitors(statins) for stroke prevention, independent of their lipid-lowering effects. Recent experimental progress indicated the effects of statins for brain protection on both vascular walls(endothelium, smooth muscle, inflammatory cells and platelets) and extra-vascular tissues(brain parenchyma). These pleiotropic effects of statins have been, at least in part, ascribed to inhibition of small GTPases Rho and Ras, which require isoprenoids (intermediates of the cholesterol biosynthesis pathway) for activation. Importantly, statin inhibition of Rho (1) attenuates the infarct size in a rat model of brain ischemia via the elevation of eNOS expression, and (2) suppresses vascular smooth muscle proliferation through up-regulation of CDK inhibitor p27kip1. The novel action of statin, as inhibitor of small GTPase family, should expand its potential toward integrative organ protection, beyond its conventional lipid-lowering and anti-atherogenic effects.",
author = "N. Sawada and Hiroshi Itoh and K. Nakao",
year = "2001",
month = "12",
language = "English",
volume = "59",
pages = "2470--2475",
journal = "Nihon rinsho. Japanese journal of clinical medicine",
issn = "0047-1852",
publisher = "Nipponrinsho Co., Inc.",
number = "12",

}

TY - JOUR

T1 - Novel actions of HMG-CoA reductase inhibitors(statins)--vascular and cerebral protection through inhibition of small GTPase Rho

AU - Sawada, N.

AU - Itoh, Hiroshi

AU - Nakao, K.

PY - 2001/12

Y1 - 2001/12

N2 - Clinical trials have demonstrated the beneficial effect of HMG-CoA reductase inhibitors(statins) for stroke prevention, independent of their lipid-lowering effects. Recent experimental progress indicated the effects of statins for brain protection on both vascular walls(endothelium, smooth muscle, inflammatory cells and platelets) and extra-vascular tissues(brain parenchyma). These pleiotropic effects of statins have been, at least in part, ascribed to inhibition of small GTPases Rho and Ras, which require isoprenoids (intermediates of the cholesterol biosynthesis pathway) for activation. Importantly, statin inhibition of Rho (1) attenuates the infarct size in a rat model of brain ischemia via the elevation of eNOS expression, and (2) suppresses vascular smooth muscle proliferation through up-regulation of CDK inhibitor p27kip1. The novel action of statin, as inhibitor of small GTPase family, should expand its potential toward integrative organ protection, beyond its conventional lipid-lowering and anti-atherogenic effects.

AB - Clinical trials have demonstrated the beneficial effect of HMG-CoA reductase inhibitors(statins) for stroke prevention, independent of their lipid-lowering effects. Recent experimental progress indicated the effects of statins for brain protection on both vascular walls(endothelium, smooth muscle, inflammatory cells and platelets) and extra-vascular tissues(brain parenchyma). These pleiotropic effects of statins have been, at least in part, ascribed to inhibition of small GTPases Rho and Ras, which require isoprenoids (intermediates of the cholesterol biosynthesis pathway) for activation. Importantly, statin inhibition of Rho (1) attenuates the infarct size in a rat model of brain ischemia via the elevation of eNOS expression, and (2) suppresses vascular smooth muscle proliferation through up-regulation of CDK inhibitor p27kip1. The novel action of statin, as inhibitor of small GTPase family, should expand its potential toward integrative organ protection, beyond its conventional lipid-lowering and anti-atherogenic effects.

UR - http://www.scopus.com/inward/record.url?scp=0035653582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035653582&partnerID=8YFLogxK

M3 - Article

C2 - 11766357

AN - SCOPUS:0035653582

VL - 59

SP - 2470

EP - 2475

JO - Nihon rinsho. Japanese journal of clinical medicine

JF - Nihon rinsho. Japanese journal of clinical medicine

SN - 0047-1852

IS - 12

ER -