Carbon Monoxide-Saturated Polymerized Placenta Hemoglobin Optimizes Mitochondrial Function and Protects Heart Against Ischemia-Reperfusion Injury
| Autor: | Hongfei Nie, Tao Li, Haiyang Yu, Wei Wu, Yarong Zhang, Yan Deng, Shen Li, Wentao Zhou, Xuewen Xu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cardiac function curve Male Glucose uptake medicine.medical_treatment Placenta Ischemia Myocardial Infarction Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Pharmacology Mitochondria Heart Wortmannin Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Hemoglobins 0302 clinical medicine Pregnancy medicine Animals Humans Insulin Respiratory function Saline Carbon Monoxide Chemistry medicine.disease Rats 030104 developmental biology Female Hemoglobin Cardiology and Cardiovascular Medicine Reperfusion injury |
| Zdroj: | Journal of cardiovascular pharmacology. 77(6) |
| ISSN: | 1533-4023 |
| Popis: | Ischemia-reperfusion (I-R) injury is detrimental to cardiovascular system. This study was designed to investigate whether carbon monoxide-saturated polymerized human placenta hemoglobin (CO-PolyPHb) attenuates cardiac I-R injury and to elucidate the underlying mechanism(s). Sixty male adult Sprague-Dawley rats were randomly divided into 6 groups: saline + sham group, PolyPHb + sham group, CO-PolyPHb + sham group, saline + I-R group, PolyPHb + I-R group, and CO-PolyPHb + I-R group. Rats were pretreated with injection of PolyPHb, CO-PolyPHb (0.5 g Hb/kg/d), or an equivalent volume of saline via caudal vein for 3 days. After pretreatment, hearts were isolated Langendorff perfused and subjected to 30-minute no-flow ischemia and 120-minute reperfusion. As compared with the saline + I-R group, pretreatment with CO-PolyPHb greatly improved the recovery of cardiac function, reduced infarct size, and suppressed the release of cardiac enzyme. Importantly, CO-PolyPHb showed more prominent cardioprotective effect than PolyPHb, exhibiting a promising therapeutic potential in cardiac I-R injury. Further study demonstrated that CO-PolyPHb activated molecular signaling toward mitophagy and significantly elevated the mitochondrial respiratory function in the heart. In addition, CO-PolyPHb upregulated the phosphorylation of the proteins in insulin signaling pathway and increased the glucose uptake rate in cardiomyocytes. Pharmacological inhibition of this pathway by wortmannin abrogated the anti-I-R effect of CO-PolyPHb. In conclusion, using an isolated rat heart model, we have demonstrated that pretreatment with CO-PolyPHb provided protective effect against cardiac I-R injury, and this protection was mediated by the improvement of mitochondrial function and activation of insulin signaling pathway in the heart. |
| Databáze: | OpenAIRE |
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