PMID- 34863716
OWN - NLM
STAT- MEDLINE
DCOM- 20220208
LR  - 20220208
IS  - 1872-8227 (Electronic)
IS  - 0168-8227 (Linking)
VI  - 183
DP  - 2022 Jan
TI  - Irisin rescues diabetic cardiac microvascular injury via ERK1/2/Nrf2/HO-1 
      mediated inhibition of oxidative stress.
PG  - 109170
LID - S0168-8227(21)00530-1 [pii]
LID - 10.1016/j.diabres.2021.109170 [doi]
AB  - AIMS: Cardiac microvascular dysfunction is a common feature across cardiovascular 
      complications in diabetes, while effective therapy remains elusive. This study 
      was designed to evaluate the effect of irisin on cardiac microvascular injury in 
      type 2 diabetes mellitus (T2DM). METHODS: T2DM was induced in C57BL/6J mice. A 
      cohort diabetic mice received a 12-week treatment of irisin. Cardiac function and 
      microvessel density were evaluated. Whether irisin directly regulates cardiac 
      microvascular endothelial cells (CMECs) function was determined in vitro. 
      Discovery-drive approaches followed by cause-effect analysis were used to 
      uncover the molecular mechanisms. RESULTS: Irisin improved cardiac function in 
      diabetic mice, and increased microvessel density. In vitro study revealed that 
      irisin promoted CMECs proliferation and reduced high glucose and high lipid 
      (HGHL)-induced apoptosis. Mechanistically, irisin increased mRNA and protein 
      levels of heme oxygenase 1 (HO-1), superoxide dismutase 1 and superoxide 
      dismutase 2, among which HO-1 ranked top. Irisin stimulated the phosphorylation 
      of extracellular regulated protein kinases (ERK) 1/2 and nuclear factor 
      erythroid-derived 2-like 2 (Nrf2) nuclear translocation, while U0126 (the 
      inhibitor of ERK1/2) inhibited irisin-induced Nrf2 nuclear translocation and HO-1 
      expression. Nrf2 siRNA inhibited irisin's antioxidative effects. CONCLUSION: 
      Irisin could rescue cardiac microvessels against oxidative stress and apoptosis 
      in diabetes via ERK1/2/Nrf2/HO-1 pathway.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Zhu, Di
AU  - Zhu D
AD  - Department of Endocrinology, Air Force Medical Center, Air Force Medical 
      University, 30 Fucheng Road, Beijing 100142, China.
FAU - Zhang, Xiaotian
AU  - Zhang X
AD  - Hospital of Troop 75600, 3002 Fuqiang Road, Shenzhen 518048, China.
FAU - Wang, Fenglin
AU  - Wang F
AD  - Department of Endocrinology, Air Force Medical Center, Air Force Medical 
      University, 30 Fucheng Road, Beijing 100142, China.
FAU - Ye, Qiao
AU  - Ye Q
AD  - Clinical Medicine Laboratory, Air Force Medical Center, Air Force Medical 
      University, 30 Fucheng Road, Beijing 100142, China.
FAU - Yang, Caizhe
AU  - Yang C
AD  - Department of Endocrinology, Air Force Medical Center, Air Force Medical 
      University, 30 Fucheng Road, Beijing 100142, China. Electronic address: 
      yangcaizhe2008@163.com.
FAU - Liu, Demin
AU  - Liu D
AD  - Department of Cardiology, Second Hospital of Hebei Medical University, 215 Heping 
      West Road, Shijiazhuang 050010, China. Electronic address: 
      liudemincardiol@163.com.
LA  - eng
PT  - Journal Article
DEP - 20211202
PL  - Ireland
TA  - Diabetes Res Clin Pract
JT  - Diabetes research and clinical practice
JID - 8508335
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Experimental
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Endothelial Cells/metabolism
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Oxidative Stress
OTO - NOTNLM
OT  - Cardiac microvascular injury
OT  - Irisin
OT  - Oxidative stress
OT  - Type 2 diabetes mellitus
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/12/06 06:00
MHDA- 2022/02/09 06:00
CRDT- 2021/12/05 20:58
PHST- 2021/08/22 00:00 [received]
PHST- 2021/11/23 00:00 [revised]
PHST- 2021/11/25 00:00 [accepted]
PHST- 2021/12/06 06:00 [pubmed]
PHST- 2022/02/09 06:00 [medline]
PHST- 2021/12/05 20:58 [entrez]
AID - S0168-8227(21)00530-1 [pii]
AID - 10.1016/j.diabres.2021.109170 [doi]
PST - ppublish
SO  - Diabetes Res Clin Pract. 2022 Jan;183:109170. doi: 10.1016/j.diabres.2021.109170. 
      Epub 2021 Dec 2.