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Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats.

Authors
  • Chien, Chen-Yen1, 2, 3
  • Wen, Ting-Jui4
  • Cheng, Yu-Hsiuan4
  • Tsai, Yi-Ting5
  • Chiang, Chih-Yao5, 6
  • Chien, Chiang-Ting4
  • 1 Department of Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan. , (Taiwan)
  • 2 Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan. , (Taiwan)
  • 3 Mackay Junior College of Medicine, Nursing and Management, New Taipei City 11260, Taiwan. , (Taiwan)
  • 4 Department of Life Science, School of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan. , (Taiwan)
  • 5 Division of Cardiovascular Surgery, National Defense Medical Center, Taipei 11490, Taiwan. , (Taiwan)
  • 6 Division of Cardiovascular Surgery, Heart Center, Cheng Hsin General Hospital, Taipei 11220, Taiwan. , (Taiwan)
Type
Published Article
Journal
Antioxidants
Publisher
MDPI AG
Publication Date
Jul 29, 2020
Volume
9
Issue
8
Identifiers
DOI: 10.3390/antiox9080679
PMID: 32751309
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Diabetes exacerbates myocardial ischemia/reperfusion (IR) injury by incompletely understood mechanisms. We explored whether diabetes diminished BAG3/Bcl-2/Nrf-2/HO-1-mediated cardioprotection and overproduced oxidative stress contributing to exaggerated IR injury. Streptozotocin-induced diabetes enhanced hyperglycemia, cardiac NADPH oxidase p22/p67 expression, malondialdehyde amount and leukocyte infiltration, altered the mesenteric expression of 4-HNE, CaSR, p-eNOS and BAG3 and impaired microvascular reactivity to the vasoconstrictor/vasodilator by a wire myography. In response to myocardial IR, diabetes further depressed BAG3/Bcl-2/Nrf-2/HO-1 expression, increased cleaved-caspase 3/poly(ADP-ribose) polymerase (PARP)/TUNEL-mediated apoptosis and exacerbated IR-induced left ventricular dysfunction characterized by further depressed microcirculation, heart rate, left ventricular systolic pressure and peak rate of pressure increase/decrease (±dp/dt) and elevated left ventricular end-diastolic pressure (LVEDP) and Evans blue-2,3,5-triphenyltetrazolium chloride-stained infarct size in diabetic hearts. Our results implicated diabetes exacerbated IR-induced myocardial dysfunction through downregulated BAG3/Bcl-2/Nrf-2/HO-1 expression, increased p22/p67/caspase 3/PARP/apoptosis-mediated oxidative injury and impaired microvascular reactivity.

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