High‑fat diet‑induced LCN2 exacerbates myocardial ischemia‑reperfusion injury by enhancing platelet activation

Li,Peng; Chen,Juhai; Wang,Mingdong; Wang,Qi; Liu,Xingde

doi:10.3892/mmr.2024.13329

High‑fat diet‑induced LCN2 exacerbates myocardial ischemia‑reperfusion injury by enhancing platelet activation

Authors:
- Peng Li
- Juhai Chen
- Mingdong Wang
- Qi Wang
- Xingde Liu
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Affiliations: Department of Pathology and Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 561113, P.R. China, Department of Internal Medicine, Guiyang Public Health Treatment Center, Guiyang, Guizhou 550003, P.R. China, Clinical Laboratory, Guiyang Public Health Treatment Center, Guiyang, Guizhou 550003, P.R. China, Department of Histology and Embryology, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 561113, P.R. China
Published online on: September 12, 2024 https://doi.org/10.3892/mmr.2024.13329
Article Number: 205
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Following acute myocardial infarction, the recovery of blood flow leads to myocardial ischemia‑reperfusion (MI/R) injury, which is primarily characterized by the activation of inflammatory signals, microvascular obstruction, increased oxidative stress and excessive Ca²⁺ overload. It has also been demonstrated that platelets can exacerbate MI/R injury by releasing reactive oxygen species, inflammatory factors and chemokines, while also obstructing microvessels through thrombus formation. As a bioactive molecule with proinflammatory and chemotactic properties, lipocalin 2 (LCN2) exhibits a positive correlation with obesity, hyperglycemia, hypertriglyceridemia and insulin resistance index, which are all significant risk factors for ischemic cardiomyopathy. Notably, the potential role of LCN2 in promoting atherosclerosis may be related to its influence on the function of macrophages, smooth muscle cells and endothelial cells, but its effect on platelet function has not yet been reported. In the present study, the effect of a high‑fat diet (HFD) on LCN2 expression was determined by detecting LCN2 expression levels in the liver and serum samples of mice through reverse transcription‑quantitative PCR and enzyme linked immunosorbent assay, respectively. The effect of LCN2 on platelet function was evaluated by examining whether LCN2 affected platelet activation, aggregation, adhesion, clot retraction and P‑selectin expression. To determine whether LCN2 aggravated MI/R injury in HFD‑fed mice by affecting platelet and inflammatory cell recruitment, wild‑type and LCN2 knockout mice fed a HFD were subjected to MI/R injury, then hearts were collected for hematoxylin and eosin staining and 2,3,5‑triphenyltetrazolium chloride staining, and immunohistochemistry was employed to detect the expression of CD42b, Ly6G, CD3 and B220. Based on observing the upregulation of LCN2 expression in mice fed a HFD, the present study further confirmed that LCN2 could accelerate platelet activation, aggregation and adhesion. Moreover, in vivo studies validated that knockout of LCN2 not only mitigated MI/R injury, but also inhibited the recruitment of platelets and inflammatory cells in myocardial tissue following ischemia‑reperfusion. In conclusion, the current findings suggested that the effect of HFD‑induced LCN2 on aggravating MI/R injury may totally or partially dependent on its promotion of platelet function.

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