标题：Deletion of P110δ promotes the development of myocarditis in ApoE-deficient mice by increasing mononuclear cell peritoneal infiltration
作者：ZHANG Q.-Z.; XUE A.-Y.; Wei W.; PANG A.-M.; CAO L.-N.; LIU F.
作者机构：[ZHANG, Q.-Z] Out-Patient Department, Second Hospital of Shandong University, Jinan, Shandong, 250000, China;[ XUE, A.-Y] Department of Cardiology, Se 更多
通讯作者地址：[LIU, F] Department of Cardiology, Second Hospital of Shandong University, 247 Beiyuan Road, China;
来源：Molecular Medicine Reports
关键词：ApoE; Apoptosis; Monocytes; Myocarditis; P110δ
摘要：Phosphoinositide 3-kinase catalytic subunit δ isoform (P110δ) is mainly expressed in white blood cells. It is involved in T and B lymphocyte differentiation, maturation and the neutrophil chemotaxis process. Apolipoprotein E (ApoE) is an arginine-rich alkaline protein, which is present in plasma chylomicron, low-density lipoprotein and very low-density lipoprotein. The present study aimed to determine the effects of P110δ deletion on myocarditis in ApoE-/- mice. A mouse model of ApoE and P110δ double deletion was initially constructed; hematoxylin and eosin (H&E) staining was performed to detect the histological alterations in the mouse myocardium. Systolic and diastolic alterations, and alterations in the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were examined by electrocardiogram. Blood cell of ApoE and P110δ double mice was used to detect changes in white blood cells and monocytes. Western blotting was used to detect the expression levels of apoptosis-associated proteins, whereas flow cytometry was used to detect the percentage of apoptosis. Morphological alterations in myocardial cells were observed under a microscope. The results of polymerase chain reaction demonstrated that double deletion mice were successfully constructed. H&E staining revealed that cells in the ApoE-/- mice were spindle-shaped; however, the nuclei were smaller in the double deletion mice. There was no change in cardiac contraction in normal mice; however, in double deletion mice, the systolic and diastolic contractions were markedly reduced. LVFS and LVEF were decreased compared with in the control group. Blood cell analysis indicated that the content of white blood cells and monocytes in the experimental group was significantly higher than that in the control group. Western blotting demonstrated that the expression levels of apoptotic proteins in double deletion mice were significantly higher compared with in the control group. Flow cytometry revealed that the apoptotic ratio was increased in double deletion mice compared with in the control group (42 vs. 21%). These findings suggested that deletion of P110δ may induce monocyte peritoneal infiltration and increase apoptosis, thus promoting the development of myocarditis. © 2020 Spandidos Publications. All rights reserved.