PMID- 30970521
OWN - NLM
STAT- MEDLINE
DCOM- 20190903
LR  - 20190903
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 112
DP  - 2019 Apr
TI  - Fenofibrate improves vascular endothelial function in diabetic mice.
PG  - 108722
LID - S0753-3322(18)32750-1 [pii]
LID - 10.1016/j.biopha.2019.108722 [doi]
AB  - Microvascular and macrovascular complications are major causes of disability and 
      death in diabetic patients. High levels of blood glucose sabotage the integrity 
      of blood vessels and induce endothelial dysfunction. Fenofibrate is an agonist of 
      peroxisome proliferator-activated receptor alpha and can reduce the incidence of 
      cardiovascular events in diabetic patients. This study tested the hypothesis that 
      fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice 
      and relieve high glucose-induced endothelial dysfunction via activating 
      endothelial nitric oxide synthase (eNOS) and adenosine monophosphate-activated 
      protein kinase (AMPK) phosphorylation. A streptozotocin (STZ)-induced diabetic 
      model was established by intraperitoneal injection of STZ (dissolved in sodium 
      citrate buffer) at a dose of 60 mg/kg for 5 consecutive days. Mice were 
      administered fenofibrate (100 mg/kg/d, i.g.) for 14 days. The endothelial 
      function of extracted mouse aortae was examined by evaluating acetylcholine 
      induced endothelium-dependent relaxation combined with phenylephrine-induced 
      vasoconstriction and sodium nitroprusside-induced endothelium-independent 
      relaxation. Superoxide onion (O(2)(-)) was determined using dihydroethidium 
      staining of aortae. Functions of mouse aortic endothelial cells (MAECs) were 
      assessed, and expression levels of eNOS and AMPK were determined by Western 
      blotting. Fenofibrate ameliorated the impaired endothelium-dependent relaxation 
      in diabetic mice and decreased the level of intracellular O(2)- in diabetic mouse 
      aortae. In-vitro, fenofibrate treatment improved the impaired function of MAECs, 
      increased nitric oxide production, and decreased the O(2)- level, as well as 
      activated eNOS and AMPK phosphorylation in cultured MAECs by high glucose. 
      Fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice 
      and relieve high glucose-induced endothelial dysfunction, which was possibly 
      related to the activation of eNOS and AMPK phosphorylation.
CI  - Copyright (c) 2019. Published by Elsevier Masson SAS.
FAU - Xin, Rujuan
AU  - Xin R
AD  - Department of Pharmacy, Shanghai Skin Disease Hospital, Shanghai, 200443, China.
FAU - An, Duopeng
AU  - An D
AD  - Department of Pharmacy, Shanghai Skin Disease Hospital, Shanghai, 200443, China.
FAU - Li, Ying
AU  - Li Y
AD  - Department of Pharmacy, Shanghai Skin Disease Hospital, Shanghai, 200443, China.
FAU - Fu, Jin
AU  - Fu J
AD  - Department of Pharmacy, Ninghai First Hospital, Zhejiang, 315600, China.
FAU - Huang, Fang
AU  - Huang F
AD  - Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, 200072, China. Electronic address: hazel_huang@126.com.
FAU - Zhu, Quangang
AU  - Zhu Q
AD  - Department of Pharmacy, Shanghai Skin Disease Hospital, Shanghai, 200443, China. 
      Electronic address: qgzhu@126.com.
LA  - eng
PT  - Journal Article
DEP - 20190227
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (PPAR alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 5W494URQ81 (Streptozocin)
RN  - IY9XDZ35W2 (Glucose)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/drug effects/physiopathology
MH  - Diabetes Mellitus, Experimental/*drug therapy/physiopathology
MH  - Diabetic Angiopathies/physiopathology/*prevention & control
MH  - Endothelial Cells/drug effects/metabolism
MH  - Endothelium, Vascular/*drug effects/physiopathology
MH  - Fenofibrate/pharmacology/*therapeutic use
MH  - Glucose/pharmacology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/metabolism
MH  - PPAR alpha/agonists
MH  - Streptozocin
MH  - Vasoconstriction/*drug effects
MH  - Vasodilation/*drug effects
OTO - NOTNLM
OT  - Diabetes
OT  - Endothelial dysfunction
OT  - Fenofibrate
OT  - Mouse aortic endothelial cells
OT  - eNOS
EDAT- 2019/04/12 06:00
MHDA- 2019/09/04 06:00
CRDT- 2019/04/12 06:00
PHST- 2018/04/25 00:00 [received]
PHST- 2019/02/14 00:00 [revised]
PHST- 2019/02/21 00:00 [accepted]
PHST- 2019/04/12 06:00 [entrez]
PHST- 2019/04/12 06:00 [pubmed]
PHST- 2019/09/04 06:00 [medline]
AID - S0753-3322(18)32750-1 [pii]
AID - 10.1016/j.biopha.2019.108722 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2019 Apr;112:108722. doi: 10.1016/j.biopha.2019.108722. Epub 
      2019 Feb 27.