PMID- 18000963
OWN - NLM
STAT- MEDLINE
DCOM- 20090107
LR  - 20080430
IS  - 0198-6325 (Print)
IS  - 0198-6325 (Linking)
VI  - 28
IP  - 4
DP  - 2008 Jul
TI  - Macrophages: an elusive yet emerging therapeutic target of atherosclerosis.
PG  - 483-544
AB  - Macrophages are central to the initiation and progression of atherosclerosis and 
      thus can be very appropriate targets for therapy. Cell adhesion molecules 
      mediating monocytes recruitment to the endothelium are attractive therapy targets 
      and their inhibitors are in clinical trials. Macrophage scavenger receptors like 
      SR-A and CD-36 mediate foam cell formation by facilitating the uptake of modified 
      lipids. Peroxisome proliferator-activated receptors (PPAR), liver X receptor 
      (LXR)-mediated signaling, mitogen-activated protein kinase (MAPK) induced 
      phosphorylation events seem to play an important role in this phenomenon. 
      Proteins affecting macrophage cholesterol metabolism and transport, including 
      ATP-binding cassette (ABC) A1, ABCG1, acyl-CoA:cholesterol acyltransferase 
      (ACAT), apolipoprotein A-1 (ApoA-1), neutral cholesteryl ester hydrolase (NCEH) 
      also regulate foam cell formation and are being developed as therapeutic targets 
      by many pharmaceutical companies. Macrophage proliferation and apoptosis are 
      important events controlling inflammatory response, plaque vulnerability, and 
      destabilization. Free cholesterol (FC) activates the macrophage endoplasmic 
      reticulum (ER) stress pathway and apoptosis. Free radicals and nitric oxide also 
      modulate macrophage foam cell formation and apoptosis. Various antioxidants like 
      AGI-1067 and BO-653 are in clinical trials for atherosclerosis treatment. 
      Macrophage matrix metalloproteinase's (MMP's) play a significant role in 
      weakening and rupture of plaques. Efforts are on to develop isoform specific MMP 
      inhibitor. CD-14, MMP-3, ABCA1, Toll-like receptor-4 (TLR-4), lectin-like 
      oxidized low-density lipoprotein receptor-1 (LOX-1), arachidonate lipoxygenase-15 
      (ALOX-15), and Connexin37 polymorphisms and macrophage dysfunction signify their 
      importance in atherosclerosis. Deciphering the role of macrophages in regulating 
      dyslipidemia and inflammation during atherosclerosis is important for developing 
      them as therapeutic targets.
CI  - (c) 2007 Wiley Periodicals, Inc.
FAU - Tiwari, R L
AU  - Tiwari RL
AD  - Division of Pharmacology, Central Drug Research Institute, Lucknow 226001, India.
FAU - Singh, V
AU  - Singh V
FAU - Barthwal, M K
AU  - Barthwal MK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Med Res Rev
JT  - Medicinal research reviews
JID - 8103150
RN  - 0 (Free Radicals)
RN  - 0 (Receptors, Scavenger)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Atherosclerosis/genetics/*pathology/*therapy
MH  - Free Radicals/metabolism
MH  - Humans
MH  - Macrophages/metabolism/*pathology
MH  - Polymorphism, Genetic
MH  - Receptors, Scavenger/metabolism
RF  - 529
EDAT- 2007/11/16 09:00
MHDA- 2009/01/08 09:00
CRDT- 2007/11/16 09:00
PHST- 2007/11/16 09:00 [pubmed]
PHST- 2009/01/08 09:00 [medline]
PHST- 2007/11/16 09:00 [entrez]
AID - 10.1002/med.20118 [doi]
PST - ppublish
SO  - Med Res Rev. 2008 Jul;28(4):483-544. doi: 10.1002/med.20118.