Recombinant extracellular domain (p75ECD) of the neurotrophin receptor p75 attenuates myocardial ischemia-reperfusion injury by inhibiting the p-JNK/caspase-3 signaling pathway in rat microvascular pericytes
| Autor: | Yunling Lin, ZhiXiong Wei, DanQing Hu, Teng Ying, DeDong Zheng, Lingzhen Wu, Xin-Fu Zhou, TingXiang Lan, Hong Huashan, Jun Fang, Lianglong Chen, ZhiWei Yang, XiaoLiang Jiang |
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| Přispěvatelé: | Fang, Jun, Wei, ZhiXiong, Zheng, DeDong, Ying, Teng, Hong, HuaShan, Hu, DanQing, Lin, YunLing, Jiang, XiaoLiang, Wu, LingZhen, Lan, TingXiang, Yang, ZhiWei, Zhou, XinFu, Chen, LiangLong |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
microvascular dysfunction Myocardial Infarction Apoptosis Coronary Artery Disease Receptor Nerve Growth Factor Ventricular Function Left law.invention Rats Sprague-Dawley 0302 clinical medicine law pericyte Coronary Heart Disease Phosphorylation Receptor Cells Cultured c-Jun N-terminal kinase Original Research 0303 health sciences biology Ventricular Remodeling Caspase 3 neurotrophin receptor extracellular domain reperfusion injury Recombinant Proteins Cell biology medicine.anatomical_structure Recombinant DNA Pericyte Signal transduction c‐Jun N‐terminal kinase Cardiology and Cardiovascular Medicine Neurotrophin Signal Transduction Myocardial Reperfusion Injury 03 medical and health sciences Extracellular medicine Animals 030304 developmental biology business.industry Myocardium JNK Mitogen-Activated Protein Kinases Recovery of Function medicine.disease Atherosclerosis Fibrosis Peptide Fragments Disease Models Animal biology.protein business Pericytes Reperfusion injury 030217 neurology & neurosurgery |
| Zdroj: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Popis: | Background Pro‐NTs (precursor of neurotrophins) and their receptor p75 are potential targets for preventing microvascular dysfunction induced by myocardial ischemia–reperfusion injury ( IRI ). p75ECD (ectodomain of neurotrophin receptor p75) may physiologically produce neurocytoprotective effects by scavenging pro‐ NT s. We therefore hypothesized that p75 ECD may have a cardioprotective effect on IRI through microvascular mechanisms. Methods and Results Myocardial IRI was induced in Sprague‐Dawley rats by occluding the left main coronary arteries for 45 minutes before a subsequent relaxation. Compared with the ischemia–reperfusion group, an intravenous injection of p75 ECD (3 mg/kg) 5 minutes before reperfusion reduced the myocardial infarct area at 24 hours after reperfusion (by triphenyltetrazolium chloride, 44.9±3.9% versus 34.6±5.7%, P NT s expression at 24 hours and 28 days after reperfusion (by Western blotting). A simulative IRI model using rat microvascular pericytes was established in vitro by hypoxia–reoxygenation (2/6 hours) combined with pro‐ NT s treatment (3 nmol/L) at R. p75 ECD (3 μg/mL) given at R improved pericyte survival (by methyl thiazolyl tetrazolium assay) and attenuated apoptosis (by terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling). In the reperfused hearts and hypoxia–reoxygenation +pro‐ NT s‐injured pericytes, p75 ECD inhibited the expression of p‐JNK (phospho of c‐Jun N‐terminal kinase)/caspase‐3 (by Western blotting). SP 600125, an inhibitor of JNK , did not enhance the p75 ECD ‐induced infarct‐sparing effects and pericyte protection. Conclusions p75 ECD may attenuate myocardial IRI via pro‐ NT s reduction‐induced inhibition of p‐ JNK /caspase‐3 pathway of microvascular pericytes in rats. |
| Databáze: | OpenAIRE |
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