@article{6dbc915aba7e48afbff1103952e2bc55,
title = "Diabetes upregulates oxidative stress and downregulates cardiac protection to exacerbate myocardial ischemia/reperfusion injury in rats",
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.",
keywords = "Apoptosis, Diabetes, Myocardial ischemia/reperfusion, Oxidative stress",
author = "Chien, {Chen Yen} and Wen, {Ting Jui} and Cheng, {Yu Hsiuan} and Tsai, {Yi Ting} and Chiang, {Chih Yao} and Chien, {Chiang Ting}",
note = "Funding Information: This work was supported by grants from the Ministry of Science and Technology (MOST 102-2320-B-003-001-MY3) (CT. Chien) and in part from the Cheng Hsin General Hospital (C-Y Chiang). Funding Information: thiCs .m-Ya.Cn.u(sCchriepnt-.YCe.n-YC.hCi.e(nC),hCe.n-Y-Y.Ce.n( CChhiihe-nY)a,oCC.-hYi.aCn.g()Cahnidh-CY.a-To. CC.hdiraanfgte) danthde Cm.a-Tn.uCs.c drirpatf.teCd.- Yth.Ce.m(Cahneuns-cYreipntC. Chi.e-n), Y.CT..-J(.CWh.e, nY-.Y-Hen.CC.,hYi.e-nT.)T, .Ta.-nJd.WC.,. -YT..C-H. .cCo.n, tYri.b-Tu.tTe.d atnodd Cis.c-Tu.sCsi.o cnonotfrtihbuetreedsutlot sd. iCsc.u-Ys.sCio.n(Cohf etnh-eY ernesCulhtsie. nC).,-CY..C-Y.. C. (Chen-Yen Chien), C.-Y.C. (Chih-Yao Chiang) and C.-T.C. contributed to the design and conduction of the study. revised the drafted manuscript. The last two authors contributed equally to this work. All authors have read and All the authors critically revised the drafted manuscript. The last two authors contributed equally to this work. agreed to the published version of the manuscript. All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by grants from the Ministry of Science and Technology (MOST Funding: This work was supported by grants from the Ministry of Science and Technology (MOST 102-2320-B-003-001-MY3) (C.T. Chien) and in part from the Cheng Hsin General Hospital (C.Y. Chiang). Conflicts of Interest: All the authors declare no conflicts of interest. Conflict of Interest: All the authors declare no conflicts of interest. Abbreviations Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = aug,
doi = "10.3390/antiox9080679",
language = "English",
volume = "9",
pages = "1--18",
journal = "Antioxidants",
issn = "2076-3921",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",
}
