PMID- 31772713
OWN - NLM
STAT- MEDLINE
DCOM- 20200410
LR  - 20220411
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2019
DP  - 2019
TI  - Plin5/p-Plin5 Guards Diabetic CMECs by Regulating FFAs Metabolism 
      Bidirectionally.
PG  - 8690746
LID - 10.1155/2019/8690746 [doi]
LID - 8690746
AB  - BACKGROUND: Hyper-free fatty acidemia (HFFA) impairs cardiac capillaries, as well 
      as type 2 diabetes mellitus (T2DM). Perilipin 5 (Plin5) maintains metabolic 
      balance of free fatty acids (FFAs) in high oxidative tissues via the states of 
      nonphosphorylation and phosphorylation. However, when facing to T2DM-HFFA, 
      Plin5's role in cardiac microvascular endothelial cells (CMECs) is not defined. 
      METHODS: In mice of WT or Plin5(-/-), T2DM models were rendered by high-fat diet 
      combined with intraperitoneal injection of streptozocin. CMECs isolated from left 
      ventricles were incubated with high glucose (HG) and high FFAs (HFFAs). Plin5 
      phosphorylation was stimulated by isoproterenol. Plin5 expression was knocked 
      down by small interfering RNA (siRNA). We determined cardiac function by small 
      animal ultrasound, apoptotic rate by flow cytometry, microvessel quantity by 
      immunohistochemistry, microvascular integrity by scanning electron microscopy, 
      intracellular FFAs by spectrophotometry, lipid droplets (LDs) by Nile red 
      staining, mRNAs by quantitative real-time polymerase chain reaction, proteins by 
      western blots, nitric oxide (NO) and reactive oxygen species (ROS) by fluorescent 
      dye staining and enzyme-linked immunosorbent assay kits. RESULTS: In CMECs, HFFAs 
      aggravated cell injury induced by HG and activated Plin5 expression. In mice with 
      T2DM-HFFA, Plin5 deficiency reduced number of cardiac capillaries, worsened 
      structural incompleteness, and enhanced diastolic dysfunction. Moreover, in CMECs 
      treated with HG-HFFAs, both ablation and phosphorylation of Plin5 reduced LDs 
      content, increased intracellular FFAs, stimulated mitochondrial beta-oxidation, 
      added ROS generation, and reduced the expression and activity of endothelial 
      nitric oxide synthase (eNOS), eventually leading to increased apoptotic rate and 
      decreased NO content, all of which were reversed by N-acetyl-L-cysteine. 
      CONCLUSION: Plin5 preserves lipid balance and cell survival in diabetic CMECs by 
      regulating FFAs metabolism bidirectionally via the states of nonphosphorylation 
      and phosphorylation.
CI  - Copyright (c) 2019 Jin Du et al.
FAU - Du, Jin
AU  - Du J
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Hou, Juanni
AU  - Hou J
AD  - Department of Gastroenterology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Feng, Juan
AU  - Feng J
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Zhou, Hong
AU  - Zhou H
AD  - Department of Respiration, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Zhao, Heng
AU  - Zhao H
AD  - Department of Function, Sichuan Petroleum General Hospital, Chengdu 610212, 
      China.
FAU - Yang, Dachun
AU  - Yang D
AUID- ORCID: 0000-0001-5462-2620
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Li, De
AU  - Li D
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Yang, Yongjian
AU  - Yang Y
AUID- ORCID: 0000-0003-1268-166X
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Pei, Haifeng
AU  - Pei H
AUID- ORCID: 0000-0003-1502-8404
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
LA  - eng
PT  - Journal Article
DEP - 20191017
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Perilipin-5)
RN  - 0 (Plin5 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 2491-17-0 (CME-Carbodiimide)
SB  - IM
MH  - Animals
MH  - CME-Carbodiimide/*metabolism
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Fatty Acids, Nonesterified/*metabolism
MH  - Gene Expression/*genetics
MH  - Mice
MH  - Perilipin-5/pharmacology/*therapeutic use
MH  - Reactive Oxygen Species/*metabolism
MH  - Transfection
PMC - PMC6854993
COIS- The authors declare that they have no competing interests.
EDAT- 2019/11/28 06:00
MHDA- 2020/04/11 06:00
PMCR- 2019/10/17
CRDT- 2019/11/28 06:00
PHST- 2019/03/12 00:00 [received]
PHST- 2019/07/23 00:00 [accepted]
PHST- 2019/11/28 06:00 [entrez]
PHST- 2019/11/28 06:00 [pubmed]
PHST- 2020/04/11 06:00 [medline]
PHST- 2019/10/17 00:00 [pmc-release]
AID - 10.1155/2019/8690746 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2019 Oct 17;2019:8690746. doi: 10.1155/2019/8690746. 
      eCollection 2019.