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MiR‐98‐5p promotes ischemia/reperfusion‐induced microvascular dysfunction by targeting NGF and is a potential biomarker for microvascular reperfusion
Author(s) -
Hu Yisen,
Xiong Jingjie,
Wen Hong,
Wei Heng,
Zeng Xiaocong
Publication year - 2021
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12657
Subject(s) - medicine , trpv1 , microcirculation , ischemia , nerve growth factor , reperfusion injury , antagomir , in vivo , myocardial infarction , cardiology , biomarker , receptor , cell culture , transient receptor potential channel , transfection , biology , microbiology and biotechnology , genetics , biochemistry
Objective This study examined the correlation between serum miR‐98‐5p levels and indices of microvascular reperfusion in patients undergoing primary percutaneous coronary intervention (pPCI) after ST‐segment elevation myocardial infarction (STEMI). Additionally, we evaluated the mechanisms by which miR‐98‐5p promoted ischemia/reperfusion (I/R)‐induced injury in both cultured cell lines and an animal model. Methods Circulating miR‐98‐5p levels were measured and compared from 171 STEMI patients undergoing pPCI, who were divided into two groups: no‐reflow and reflow. The levels of miR‐98‐5p, nerve growth factor (NGF), and transient receptor potential vanilloid 1 (TRPV1) were analyzed in cultured human coronary endothelial cells (HCECs) exposed to hypoxia/reoxygenation (H/R). The effects of antagomir‐98‐5p on myocardial I/R‐induced microvascular dysfunction in vivo were evaluated. Target gene expression and activity were assessed. Results Higher miR‐98‐5p levels were associated with compromised indices of microvascular reperfusion. In vitro experiments on HCECs showed that exposure to H/R significantly increased miR‐98‐5p levels. We identified NGF as a novel target of miR‐98‐5p. Further, antagomir‐98‐5p relieved microvascular dysfunction and enhanced the expression of NGF and TRPV1 in the rat myocardial I/R model. Conclusions MiR‐98‐5p promotes microvascular dysfunction by targeting the NGF‐TRPV1 axis. Serum miR‐98‐5p serves as a potential biomarker for microvascular reperfusion.