PMID- 26551391
OWN - NLM
STAT- MEDLINE
DCOM- 20171229
LR  - 20220330
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 82
IP  - 5
DP  - 2016 Nov
TI  - Potential therapeutic effects of mTOR inhibition in atherosclerosis.
PG  - 1267-1279
LID - 10.1111/bcp.12820 [doi]
AB  - Despite significant improvement in the management of atherosclerosis, this slowly 
      progressing disease continues to affect countless patients around the world. 
      Recently, the mechanistic target of rapamycin (mTOR) has been identified as a 
      pre-eminent factor in the development of atherosclerosis. mTOR is a 
      constitutively active kinase found in two different multiprotein complexes, 
      mTORC1 and mTORC2. Pharmacological interventions with a class of macrolide 
      immunosuppressive drugs, called rapalogs, have shown undeniable evidence of the 
      value of mTORC1 inhibition to prevent the development of atherosclerotic plaques 
      in several animal models. Rapalog-eluting stents have also shown extraordinary 
      results in humans, even though the exact mechanism for this anti-atherosclerotic 
      effect remains elusive. Unfortunately, rapalogs are known to trigger diverse 
      undesirable effects owing to mTORC1 resistance or mTORC2 inhibition. These 
      adverse effects include dyslipidaemia and insulin resistance, both known triggers 
      of atherosclerosis. Several strategies, such as combination therapy with statins 
      and metformin, have been suggested to oppose rapalog-mediated adverse effects. 
      Statins and metformin are known to inhibit mTORC1 indirectly via 5' adenosine 
      monophosphate-activated protein kinase (AMPK) activation and may hold the key to 
      exploit the full potential of mTORC1 inhibition in the treatment of 
      atherosclerosis. Intermittent regimens and dose reduction have also been proposed 
      to improve rapalog's mTORC1 selectivity, thereby reducing mTORC2-related side 
      effects.
CI  - (c) 2015 The British Pharmacological Society.
FAU - Kurdi, Ammar
AU  - Kurdi A
AD  - Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
FAU - De Meyer, Guido R Y
AU  - De Meyer GR
AD  - Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
FAU - Martinet, Wim
AU  - Martinet W
AD  - Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium. 
      wim.martinet@uantwerpen.be.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20151229
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*drug therapy
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
MH  - Mechanistic Target of Rapamycin Complex 1/*antagonists & inhibitors/physiology
MH  - Metformin/therapeutic use
MH  - Models, Biological
MH  - Protein Kinase Inhibitors/adverse effects/pharmacology/therapeutic use
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/physiology
PMC - PMC5061792
OTO - NOTNLM
OT  - atherosclerosis
OT  - mTOR
OT  - metformin
OT  - rapalogs
OT  - rapamycin
EDAT- 2015/11/10 06:00
MHDA- 2017/12/30 06:00
PMCR- 2017/11/01
CRDT- 2015/11/10 06:00
PHST- 2015/09/17 00:00 [received]
PHST- 2015/11/03 00:00 [revised]
PHST- 2015/11/04 00:00 [accepted]
PHST- 2015/11/10 06:00 [pubmed]
PHST- 2017/12/30 06:00 [medline]
PHST- 2015/11/10 06:00 [entrez]
PHST- 2017/11/01 00:00 [pmc-release]
AID - BCP12820 [pii]
AID - 10.1111/bcp.12820 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2016 Nov;82(5):1267-1279. doi: 10.1111/bcp.12820. Epub 2015 
      Dec 29.