Lorkowska–Zawicka B and Jawień J*

Department of Pharmacology, Jagiellonian University School of Medicine, Krakow, Poland

*Corresponding Author: Jawień J, Department of Pharmacology, Jagiellonian University School of Medicine, Krakow, Poland.

Received: May 01, 2021; Published: May 25, 2021

Abstract

  Due to apolipoprotein E - knockout mouse model of athroclerosis several new questions about atherogenesis have been recently answered. This review mainly focuses on two types of cells: one „atypical” for atherogenesis: neutrophils and one "typical”: macrophages.

  New studies suggest important roles for NETs (Neutrophil extracellular traps). Smooth muscle cells in plaque can recruit neutrophils, which undergo NETosis. NET-derived histone H4 is able to cause the lysis of smooth muscle cells. All may result in rupture of plaque.

  Neutrophils are recruited by GM-CSF to the ischemic place and there they can develop proteolysis. It was also shown that neutrophil depletion can reduce the size of myocardial infarction. Neutrophils can cause the healing after myocardial infarction, They do it by releasing neutrophil gelatinase-associated lipocalin (NGAL). Thus neutrophil contribute to the development of M2 macrophages.

  Recent studies showed that hyperlipidemia-triggered neutrophilia may induce early stages of atherogenesis. Clinical studies have previously showed a correlation between neutrophil and the risk for events. Hypercholesterolemia induces G-CSF, the very important cytokine in granulopoiesis. G-CSF decreases bone marrow CXCL12 levels, reducing the clearance of aged neutrophils. On the other hand, hypercholesterolemia increases CXCL1 levels. This unables neutrophil mobilization via CXCR2. To sum up, hyperlipidemia disturbs cytokine system controlling neutrophil homeostasis, increasing peripheral neutrophil counts.

  Atherosclerosis is characterized by an imbalance between pro-resolving and pro-inflammatory mediators, such as leukotrienes, leading to defective resolution of inflammation, tissue injury and damage-associated molecular pattern (DAMP)-mediated inflammation. The ratio of pro-resolving lipid mediators to leukotrienes is low in advanced vs early atherosclerotic plaques, and a low resolvin D1 (RvD1): leukotriene B4 ratio in saliva can predict carotid intimal thickness in humans. Similarly in mice, the advanced atherosclerotic lesions are deficient in pro-resolving lipid mediators.

  Since 1992 the mouse has become a new model for atherogenesis - namely apolipoprotein E - knockout (ApoE-KO) mice were developed. It is the only murine model that develops lesions on chow diet. It was said that apoE - knockout mice model has changed the face of atherogenesis [1].

  Currently, thanks to ApoE-KO several questions about atherosclerosis was answered. Following review will mainly focus on two types of cells: one "atypical”: neutrophils and one „typical”: macrophages [2].

Keywords: ApoE-KO; Atherosclerosis; Neutrophils

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Citation

Citation: Lorkowska–Zawicka B and Jawień J. “ApoE-Knockout Mice: What are New Achievements of this Model of Atherosclerosis?". Acta Scientific Pharmaceutical Sciences 5.6 (2020): 111-116.

Copyright

Copyright: © 2020 Lorkowska–Zawicka B and Jawień J. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.