PMID- 23285083
OWN - NLM
STAT- MEDLINE
DCOM- 20130611
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Proteomic analysis of aorta and protective effects of grape seed procyanidin B2 
      in db/db mice reveal a critical role of milk fat globule epidermal growth 
      factor-8 in diabetic arterial damage.
PG  - e52541
LID - 10.1371/journal.pone.0052541 [doi]
LID - e52541
AB  - BACKGROUND: Atherosclerosis is one of the major complications of type 2 diabetic 
      patients (T2DM), leading to morbidity and mortality. Grape seed procyanidin B2 
      (GSPB2) has demonstrated protective effect against atherosclerosis, which is 
      believed to be, at least in part, a result of its antioxidative effects. The aim 
      of this study is to identify the target protein of GSPB2 responsible for the 
      protective effect against atherosclerosis in patients with DM. METHODS AND 
      RESULTS: GSPB2 (30 mg/kg body weight/day) were administrated to db/db mice for 10 
      weeks. Proteomics of the aorta extracts by iTRAQ analysis was obtained from db/db 
      mice. The results showed that expression of 557 proteins were either up- or 
      down-regulated in the aorta of diabetic mice. Among those proteins, 139 proteins 
      were normalized by GSPB2 to the levels comparable to those in control mice. Among 
      the proteins regulated by GSPB2, the milk fat globule epidermal growth factor-8 
      (MFG-E8) was found to be increased in serum level in T2DM patients; the serum 
      level of MFG-E8 was positively correlated with carotid-femoral pulse wave 
      velocity (CF-PWV). Inhibition of MFG-E8 by RNA interference significantly 
      suppressed whereas exogenous recombinant MFG-E8 administration exacerbated 
      atherogenesis the db/db mice. To gain more insights into the mechanism of action 
      of MFG-E8, we investigated the effects of MFG-E8 on the signal pathway involving 
      the extracellular signal-regulated kinase (ERK) and monocyte chemoattractant 
      protein-1 (MCP-1). Treatment with recombinant MFG-E8 led to increased whereas 
      inhibition of MFG-E8 to decreased expression of MCP-1 and phosphorylation of 
      ERK1/2. CONCLUSION: Our data suggests that MFG-E8 plays an important role in 
      atherogenesis in diabetes through both ERK and MCP-1 signaling pathways. GSPB2, a 
      well-studied antioxidant, significantly inhibited the arterial wall changes 
      favoring atherogenesis in db/db mice by down-regulating MFG-E8 expression in 
      aorta and its serum level. Measuring MFG-E8 serum level could be a useful 
      clinical surrogate prognosticating atherogenesis in DM patients.
FAU - Yu, Fei
AU  - Yu F
AD  - Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of 
      Geriatrics, Qi-Lu Hospital of Shandong University, Jinan, China.
FAU - Li, Bao-ying
AU  - Li BY
FAU - Li, Xiao-li
AU  - Li XL
FAU - Cai, Qian
AU  - Cai Q
FAU - Zhang, Zhen
AU  - Zhang Z
FAU - Cheng, Mei
AU  - Cheng M
FAU - Yin, Mei
AU  - Yin M
FAU - Wang, Jun-fu
AU  - Wang JF
FAU - Zhang, Jian-hua
AU  - Zhang JH
FAU - Lu, Wei-da
AU  - Lu WD
FAU - Zhou, Rui-hai
AU  - Zhou RH
FAU - Gao, Hai-qing
AU  - Gao HQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121221
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Surface)
RN  - 0 (Biflavonoids)
RN  - 0 (Blood Glucose)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Grape Seed Extract)
RN  - 0 (Grape Seed Proanthocyanidins)
RN  - 0 (MFGE8 protein, human)
RN  - 0 (Mfge8 protein, mouse)
RN  - 0 (Milk Proteins)
RN  - 0 (Proanthocyanidins)
RN  - 0 (Proteome)
RN  - 0 (Triglycerides)
RN  - 29106-49-8 (procyanidin B2)
RN  - 8R1V1STN48 (Catechin)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Antigens, Surface/blood/*metabolism
MH  - Aorta/drug effects/*metabolism/*pathology/ultrastructure
MH  - Biflavonoids/pharmacology/*therapeutic use
MH  - Blood Glucose/drug effects
MH  - Body Weight/drug effects
MH  - Cardiotonic Agents/pharmacology/therapeutic use
MH  - Catechin/pharmacology/*therapeutic use
MH  - Cholesterol/blood
MH  - Computational Biology
MH  - Diabetes Mellitus, Experimental/blood/*drug therapy/pathology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fasting/blood
MH  - Glycation End Products, Advanced/blood
MH  - Grape Seed Extract/pharmacology/therapeutic use
MH  - Humans
MH  - Isotope Labeling
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Milk Proteins/blood/*metabolism
MH  - Proanthocyanidins/pharmacology/*therapeutic use
MH  - Proteome/metabolism
MH  - *Proteomics
MH  - RNA Interference/drug effects
MH  - Triglycerides/blood
PMC - PMC3528673
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/04 06:00
MHDA- 2013/06/12 06:00
PMCR- 2012/12/21
CRDT- 2013/01/04 06:00
PHST- 2012/08/07 00:00 [received]
PHST- 2012/11/15 00:00 [accepted]
PHST- 2013/01/04 06:00 [entrez]
PHST- 2013/01/04 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
PHST- 2012/12/21 00:00 [pmc-release]
AID - PONE-D-12-23550 [pii]
AID - 10.1371/journal.pone.0052541 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e52541. doi: 10.1371/journal.pone.0052541. Epub 2012 Dec 21.