PMID- 29077145
OWN - NLM
STAT- MEDLINE
DCOM- 20180727
LR  - 20211204
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 21
IP  - 19
DP  - 2017 Oct
TI  - Rosuvastatin promotes the differentiation of peripheral blood monocytes into M2 
      macrophages in patients with atherosclerosis by activating PPAR-gamma.
PG  - 4464-4471
LID - 13523 [pii]
AB  - OBJECTIVE: To evaluate M2 marker changes in human circulating monocytes before 
      and after rosuvastatin treatment, and to investigate the effects of rosuvastatin 
      on the differentiation of monocytes into M2 macrophages by activating peroxisome 
      proliferator-activated receptor-gamma (PPAR-gamma). PATIENTS AND METHODS: A total of 20 
      patients was administrated with rosuvastatin. The human peripheral blood 
      mononuclear cells (PBMCs) were extracted by Ficoll-Hypaque density gradient 
      centrifugation method. PPAR-gamma, CD206 and CD163 mRNA levels were detected by 
      Real-time polymerase chain reaction (RT-PCR). The total content of tumor necrosis 
      factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), PPAR-gamma, 
      extracellular signal-regulated kinase (ERK) and p38 Mitogen-activated protein 
      kinase (MAPK) and the contents of phosphorylated ERK and p38 MAPK were determined 
      by enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression levels of 
      CD206, Interleukin 10 (IL-10), and chemokine (C-C motif) ligand 18 (CCL18) were 
      significantly improved by rosuvastatin. The expression level of PPAR-gamma in 
      circulating monocytes was also distinctly up-regulated through the treatment with 
      rosuvastatin. After rosuvastatin therapy, PPAR-gamma mRNA expression was unceasingly 
      increased with time prolonging. The tendency of mRNA level of aP2 was the same as 
      that of PPAR-gamma. In vitro experiments indicated that in M2 macrophages, 
      rosuvastatin could enhance the decrease of CD163 expression level induced by 
      interleukin 4 (IL-4). M1 macrophages cultured by supernatant that was used to 
      culture M2 macrophages could significantly inhibit TNF-alpha and MCP-1 expressions. 
      Rosuvastatin could remarkably induce the phosphorylation of p38 MAPK, but the 
      effect on ERK1/2 was not obvious. CONCLUSIONS: Our results confirmed expressions 
      of M2 markers in human circulating peripheral blood monocytes after rosuvastatin 
      therapy. Both in vivo and in vitro experiments proved that rosuvastatin can 
      induce the expression and activation of PPAR-gamma in human monocytes, resulting in 
      the differentiation of monocytes into M2 macrophages.
FAU - Zhang, T
AU  - Zhang T
AD  - Cardiology Center of Suzhou Kowloon Hospital, Shanghai Jiaotong University, 
      Suzhou, China. ximenxiaobaozi@sina.com.
FAU - Shao, B
AU  - Shao B
FAU - Liu, G-A
AU  - Liu GA
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (Biomarkers)
RN  - 0 (CD163 antigen)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, Cell Surface)
RN  - 83MVU38M7Q (Rosuvastatin Calcium)
SB  - IM
MH  - Antigens, CD/biosynthesis/genetics
MH  - Antigens, Differentiation, Myelomonocytic/biosynthesis/genetics
MH  - Atherosclerosis/*pathology
MH  - Biomarkers/analysis
MH  - Cell Differentiation/drug effects
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Lectins, C-Type/biosynthesis/genetics
MH  - Macrophages/*drug effects
MH  - Mannose Receptor
MH  - Mannose-Binding Lectins/biosynthesis/genetics
MH  - Monocytes/*drug effects
MH  - PPAR gamma/*agonists/biosynthesis
MH  - Receptors, Cell Surface/biosynthesis/genetics
MH  - Rosuvastatin Calcium/*pharmacology
MH  - Up-Regulation/drug effects
EDAT- 2017/10/28 06:00
MHDA- 2018/07/28 06:00
CRDT- 2017/10/28 06:00
PHST- 2017/10/28 06:00 [entrez]
PHST- 2017/10/28 06:00 [pubmed]
PHST- 2018/07/28 06:00 [medline]
AID - 13523 [pii]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2017 Oct;21(19):4464-4471.