Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats
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 enh...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/8/679 |
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| author | Chen-Yen Chien Ting-Jui Wen Yu-Hsiuan Cheng Yi-Ting Tsai Chih-Yao Chiang Chiang-Ting Chien |
| author_facet | Chen-Yen Chien Ting-Jui Wen Yu-Hsiuan Cheng Yi-Ting Tsai Chih-Yao Chiang Chiang-Ting Chien |
| author_sort | Chen-Yen Chien |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:07:38Z |
| format | Article |
| id | doaj.art-d690e064f02842ba8fb941bf6402ac4c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T18:07:38Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-d690e064f02842ba8fb941bf6402ac4c2023-11-20T08:23:48ZengMDPI AGAntioxidants2076-39212020-07-019867910.3390/antiox9080679Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in RatsChen-Yen Chien0Ting-Jui Wen1Yu-Hsiuan Cheng2Yi-Ting Tsai3Chih-Yao Chiang4Chiang-Ting Chien5Department of Surgery, Mackay Memorial Hospital, Taipei 10449, TaiwanDepartment of Life Science, School of Life Science, National Taiwan Normal University, Taipei 11677, TaiwanDepartment of Life Science, School of Life Science, National Taiwan Normal University, Taipei 11677, TaiwanDivision of Cardiovascular Surgery, National Defense Medical Center, Taipei 11490, TaiwanDivision of Cardiovascular Surgery, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Life Science, School of Life Science, National Taiwan Normal University, Taipei 11677, TaiwanDiabetes 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.https://www.mdpi.com/2076-3921/9/8/679diabetesmyocardial ischemia/reperfusionoxidative stressapoptosis |
| spellingShingle | Chen-Yen Chien Ting-Jui Wen Yu-Hsiuan Cheng Yi-Ting Tsai Chih-Yao Chiang Chiang-Ting Chien Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats Antioxidants diabetes myocardial ischemia/reperfusion oxidative stress apoptosis |
| title | Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats |
| title_full | Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats |
| title_fullStr | Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats |
| title_full_unstemmed | Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats |
| title_short | Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats |
| title_sort | diabetes upregulates oxidative stress and downregulates cardiac protection to exacerbate myocardial ischemia reperfusion injury in rats |
| topic | diabetes myocardial ischemia/reperfusion oxidative stress apoptosis |
| url | https://www.mdpi.com/2076-3921/9/8/679 |
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